PHYSIO LEC CHAP 5 Electrical Signals in Neurons

Excitable cells: neurons, muscle cells, endocrine cells, fertilized eggs, some
Membrane potential- voltage difference across cell membranes maintained
plant cells, and some unicellular organisms.
by active transport of ions in animal cells

Excitable cells- rapidly alter their membrane potential by altering the

distribution of ions across the membrane.

- Use the resulting changes in the membrane potential as

communication signals, often across long distances.
- Neurons: specialized to carry electrical signals, often across long
distances.

Motor neurons- communication from CNS to the muscle (an example of

signaling function.

Dendrites- fine, branching extensions of the neuron, originating at the cell

body.

- “dendron”: tree
- Sensing incoming signals, converting these signals to an electrical
signal form of a change in the membrane potential, and
transmitting the signal to the cell body.

Cell body- contains the nucleus and protein synthetic machinery of the cell, as
well as most of the organelles, although mitochondria are also found in the
dendrites and the axon terminal.

- Also contain receptors, and thus participate in detecting incoming

signals.
- First functional zone of a motor neuron together with dendrites.

Axon hillock- second functional zone

- Located at junction of the cell body and the axon.

- Where the incoming signals from the dendrites and cell body are
conducted to.
- If signal is sufficiently large, a specialized electrical signal termed
action potential is initiated.
Axon- long slender extension leading off the cell body at the axon hillock
where action potential occurs.
- Third functional zone of the neuron
- Specialized for signal conduction.
- Often quite short but those of motor neurons of large mammals
can be several meters long (giraffe: 3 meters long).
o Each neuron has only a single axon, although the axon may branch
into several collaterals.
Myelin sheath- wrapped vertebrate motor neurons which increases the speed
of conduction of electrical impulses to the axon terminals.
Axon terminals- make up the fourth functional zone of the neuron
- specialized for signal transmission to target cells.
- Motor neuron: end of axon branches form several axon terminals.
- Swelling of the end of the axon that forms a synapse with the target
skeletal muscle cell.
o At the axon terminal of a motor neuron, the electrical signal is
transduced into a chemical signal in the form of a chemical
neurotransmitter.
o The neurotransmitter diffuses across synapse and binds to specific
receptors on the muscle cell membrane, initiating a signal in the
muscle cell and causing the muscle to contract.
Neurons are the only excitable cells specialized to use changes in membrane
potential to communicate signals across long distances.
- It is the property of excitability that gives neurons the ability to
store, recall and distribute information.
- When cell is not involved in sending an electrical signal, this voltage
difference is termed the resting membrane potential difference or
resting membrane potential (Vm) = -70 mV relative voltage to the
outside of the cell (inside of the cell membrane is 70 mV more
negatively charged than the outside of the membrane).
Ionic concentration gradients and permeability establish membrane
potential
Two factors required to establish a potential difference across a membrane:
1. Concentration gradient for an ion
2. Membrane that is permeable to it
Interior of the cell: 100 mM KCl and 10 mM NaCl
Extracellular fluid: 100 mM NaCl and 10 KCl
= conc. gradient for K (100 inside) favors outward movement, while Na (100
mM out 10 mM in) favors inside movement.
= no gradient for Cl because it’s 110 mM both in and out and solution is
electroneutral with equal numbers of anions and cations.
With channels that only allow passage for K+

o Conc gradient will cause K+ to move out of the cell along the con
SIGNALING IN A VERTEBRATE MOTOR NEURON gradient, creating a local region of electronegativity on the inner
face of the membrane (where K+ left) and electro positivity on the
Overall process: receiving an incoming signal  converting that signal to a
outer face of membrane (where K+ appeared).
change in the membrane potential  triggering action potentials that conduct
o This excess (-) charge at the inside face generates an electrical force
the signal across long distances transmitting signal to target cells in the form
of neurotransmitter. that tends to draw positive charges back into the cell.
 o As more K+ leaves the cell, the electrical force gradually increases Example: resting potential: -70 mV set voltage-clamp @ -70 mV
to a level that exactly balances the driving force from K+ conc
gradient. - If cell is at RMP = no current will be injected through the
microelectrode.
= equilibrium potential for that ion (Eion)
Example: introduce into fluid bathing the cell a neurotransmitter that binds to
= equilibrium potential is equivalent to resting membrane potential a specific Na+ channel  neurotransmitter will bind and cause the Na+
(Eion= Vm) channel to open  Na+ ions will enter the cell causing depolarization 
apparatus takes measurement if the MP and injects current to hold the
Nernst equation calculates equilibrium potential of an ion membrane at RMP despite influx of Na+.
𝑅𝑇 [𝑋]𝑜𝑢𝑡𝑠𝑖𝑑𝑒
𝐸𝑖𝑜𝑛 = 𝑙𝑛 ; where R- gas constant, T- in Kelvin, z- valence of - Analogous to thermostatically controlled heater operating by
𝑧𝐹 [𝑋]𝑖𝑛𝑠𝑖𝑑𝑒
ion, F- Faraday’s constant (96,485 J/V.mol), [X]- conc. negative feedback.
- Properties of a whole cell, or large region of a membrane.
𝐸𝐾 = −60 𝑚𝑉
Patch clamping- also used to study ion channel function.
- Equilibrium potential is called reversal potential for that ion
- The localization of the charge difference adjacent ot the membrane - Properties of single
arises because the cell membrane acts as a capacitor. channels
- Device containing 2 electrically conductive materials separated by - The experimenter
an insulator, thin layer of a nonconductive materials. fuses the top of a glass
micropipette to the
Cytoplasm and EC fluid- conducting materials. plasma membrane to act
as a recording electrode.
Lipid bilayer- insulator - The region of the
membrane within the
- Excess (+) charge outside the membrane attracts the excess (-) patch is extremely small
charge along intracellular face of the membrane. and usually contains only a
- Membrane potential only occurs in the area immediately adjacent single ion channel.
to the membrane, and bulk of the liquid in the cytoplasm and
extracellular fluid is not electrically charged.

Goldman equation calculates membrane potential

o Represents sum of the equilibrium potentials for all of the relevant

ions, with a weighting factor that takes into account the relative
permeabilities of the ion (𝑃𝑖𝑜𝑛 ).
o Influence of each ion in the overall membrane potential is
proportional to its permeability. Signals in the Dendrites and Cell Body
o Experimentally, it is easier to measure relative permeability of ions
Neurotransmitter binding- to a specific ligand-gated receptor causes ion
than absolute permeability. Thus, the Goldman equation is often
channels in the membrane to open or close, changing the permeability of the
rewritten using RP (by dividing each permeability term by 𝑃𝐾 ).
membrane and altering movement of ions (graded potentials).
o Similar to previous discussion (See Chap 3)
Graded potentials vary in magnitude
Na/K ATPase maintains membrane potential
- Depends on the strength of the stimulus.
- Electrogenic pump
- Contributes to only a small part of the resting membrane potential Strong stimulus (high conc of neurotransmitter)- increases the probability that
(approx. -10 mV) a given ion channel will open, thus causing more channels to open, keeping
them open for a longer time.
Cell membranes have an intrinsic permeability to ions, even at rest, due to leak
channels. o No neurotransmitter: ligand-gated ion channels on the surface of
the dendrite remain closed, no ions can move across the
- Needed to compensate for leakage of Na and K ions
membrane through those channels: MP= same.
- If inhibited (ouabain, digitalis), the membrane potential will slowly
o Low con: few ion channels open = small change in MP
decay = 0 mV
o High conc: more channels open = huge change in MP = amplitude
- Important to be maintained because in excitable cells undergo
of the graded potential directly reflects the strength of incoming
large increase in membrane potential during signaling.
stimulus.
Changes in membrane permeability cause electrical signals
Graded potentials are short-distance signals
Depolarization- charge difference bet inside and outside of the cell membrane
Conduction with decrement- decrease in strength as they get farther away
decreases.
from the opened ion channel.
- Membrane potential becomes less negative
- Either + charged ions entering cell or – ions moving out of the cell.

Hyperpolarization- membrane potential becomes more (-)

Repolarization- cell membrane turns toward resting membrane potential.

Ion channel function can be studied using voltage clamp

Voltage clamp- hold the voltage across a membrane at a constant level by

injecting current into the cell via a microelectrode any time the voltage across
the membrane changes.
 o A neurotransmitter opens ligand-gated Na+ channels in one
dendrite, causing Na+ to enter the dendrite and depolarizing the
area of the membrane.

Electronic current spread- positive charge spreading through the cell 

depolarization.

- Positive charges attract negative charges and repel positives, o In the other dendrite, a neurotransmitter also opens a ligand-gated
causing positive molecules to spread away from the site of initial Na+ channel, but again this depolarization is not sufficient to trigger
depolarization along the membrane. action potential.

Why does it decrease? = both of these travel to axon hillock and meet, summing up together to result
in net depo that exceeds threshold pot. and triggers action pot.
1. Leakage of charged ions across cell membrane
2. Electrical resistance of the cytoplasm - Can also prevent action potential generation. For example: in one
3. Electrical properties of the membrane dendrite there is suprathreshold pot but in the other, a neurotrans
opened K+ channels causing K+ ions to leave = hyperpolarization. =
Graded potentials can trigger action potentials at the axon hillock no movement bc balanced.

Action potential- transmit information across distances without degrading.
- Triggered by net graded potential at the membrane of the axon
hillock (trigger zone)
- If a graded potential causes the membrane potential at the axon
hillock to depolarize beyond the threshold potential (-55mV), the
axon will fire an action potential.
Temporal summation- depo that occur at two slightly different times can also
combine to determine the net change in membrane potential at the axon
hillock. (Fig 5.11)
2 depo: E1 and E2 (each of 10 mV): if E2 occurs after depolarization E1 has died
out, then maximum depolarization is 10 mV, which is not large enough to
trigger an action potential

Subthreshold potential- a graded potential that is not large enough to trigger
an action potential
Suprathreshold potential- even larger than needed to trigger an action
potential. (Figure 5.9)
Depolarizing graded potential- moves the membrane potential at the axon
hillock closer to the threshold potential.
In contrast, if depo E2 occurs before E1 has died out, 2 depo build on each
other and result in an increased net depo build on each other and result in an
increased net depo to a max of 20 mV, bringing cell from RMP of -70 mV
beyond the threshold potential of -55mV
= triggering action pot
Axon hillock- decision point for the neuron.

- Excitatory potential
- Makes an action potential more likely to occur by bringing the
membrane potential closed to the threshold potential

Hyperpolarizing graded potential- moves the membrane potential at the axon

hillock farther from the threshold potential.

- Inhibitory potential
- Makes an action potential less likely to occur by taking membrane
potential farther from the threshold potential

Graded potentials can be integrated across time and space

Spatial summation- graded potentials from different sites can interact with
each other to influence the net change in membrane potential at the axon
hillock.
 2. A suprathreshold depolarizing graded pot  activation gate open 
allowing Na+ entry.
3. Opening of activation gate increases permeability to Na+  more NA+
enters the cell  more v-g-c open  axonal membrane potential rapidly
becomes less neg  membrane pot approaches equi pot for Na+ 
electrochemical gradient for Na+ movement decreases  Na+ entry
slows.
4. Time dependent conformational change occurs in channel  closes
inactivation gate  no Na+ entry  depolarization termination
5. In response to rapid repolarization of membrane, the channel returns to
its original site.

Fig 5.14

Voltage-gated K+ channels open slowly

Threshold depolarization of the membrane at axon hillock increases the

probability that v-g K+ channels will open.

o K+ channels open  increase permeability to K+ ions  K+ ions

Signals in the Axon
3 phases of action potential
1. Depolarization phase- triggered when the membrane potential at
the axon hillock reaches threshold (as a result of summed graded
potential at the axon hillock).
- Once the hillock reached threshold, adjacent axonal membrane
quickly depolarizes reaching a positive membrane potential of
about +30 mV.
2. Repolarization phase- membrane potential rapidly returns to RMP.
3. After-hyperpolarization- membrane potential becomes even more
negative than RMP, and may approach K+ equilibrium potential (2-
15msec)
Absolute refractory period- coincides with repo and depo phases, the axon is
incapable of generating new action pot, no matter how strong the stimulus.
leave cell in response to electrochemical driving force 
intracellular side becomes more (-) (repo phase of action pot)
 V-g-c close slowly and may stay open after reaching RMP of -
70 mV (equi pot for K+ is -90 mV)  ions continue to move
out of the cell until it is hyperpolarized, accounting for after-
hyperpolarization (squid axon).
Both Na+ and K+ shape the action potential
- Refer to the figure on the next page
Action potentials transmit signals across long distances
All-or-none- allows neurons to transmit electrical signals across long distances
- Once an action potential has been initiated by opening a sufficient
no of v-g Na+ channels, it always proceeds to its conclusion and
never stops halfway through.

Relative refractory period- coincides with after-hyperpolarization, a new

action potential can be generated, but only by a large stimulus.

Voltage-gated channels generate the action potential

o Changes in membrane potential change the shape of voltage-gated

ion channels, allowing ions to move across the membrane.
o Giant axon of squid: opening of voltage-gated Na+ channels causes
depo and opening of K+ channels initiates repo and hyperpo. (Fig.
5.12)

Voltage-gated Na+ channels open at threshold potential

o Membrane potential at axon hillock approaches threshold

potential at -55mV, v-g Na+ channels begin to open, changing
permeability of membrane to Na+ ions.

Open probability of the channel- depends on size of graded potential.

A positive feedback loop drives depolarization phase

Hodgkin cycle

o Na+ influx from 1st v-g channels to open in response to the graded
potential further depolarizes the local region of the membrane,
further increasing the probability that v-g Na+ channels will open.
o Density of v-g-c in the membrane must be high in order for
+ feedback mechanism of the action pot to function.
o Mostly occurs in axon, where v-g Na+ channels are usually high in
conc.
o If remained open, Na+ ions would enter until membrane pot is
reached (+55 mV: equi pot for Na+)

Voltage-gated Na+ channels have 2 gates

1. Neuron is at RMP  the activation gate closes v-g-Na+ channels 

preventing Na+ entry.
 - Individual action pots. do not actually travel along axon: action pot - Fig. 5.20: subthreshold stimulus does not trigger an act pot.
in one part of the axon triggers other action pot in adjacent areas whereas brief stimulus at threshold might trigger a single action
of axonal membrane. potential.
- Conduction of an action pot along axon represents combination of - If threshold stimulus continues longer than the absolute and
action pot occurring at spec points along axons and local flow of relative refractory periods, additional act pots are generated.
ions and electrical current along axon, triggers action pot. further
downstream. The max. frequency at which act pot can be generated is limited by the length
of the ARP, during which new act pot cannot be generated regardless of the
1. Na+ ions enter strength of signal.
2. depolarize section of the membrane immediately surrounding the
channel - 500-1000 per sec in mammalian neurons
3. electrotonic current spread along the axon
4. membrane in adj. region of axon reaches threshold potential
5. v-g Na+ channels open Signals Across the Synapse
6. triggers another action pot.
Presynaptic cell- transmits the signal
Caenorhabditis elegans- genome lacks Na+ channels
Postsynaptic cell- receives the signal
- do not produce action potential
- use gradient potential instead. Synaptic cleft- space separating the two.

Vertebrate motor neurons are myelinated - Neuromuscular junction: synapse bet. motor neuron and a skeletal
muscle cell.
Schwann cells- specialized lipid-rich cells form the myelin sheath by wrapping
in a spiral pattern around the axon of the neuron. Intracellular Ca2+ regulates neurotransmitter release

- May wrap long axons, separated by areas of exposed axonal

membrane called nodes of Ranvier (contain high densities of
voltage-gated channels.
- Internodes: myelinated regions.
- Collectively known as glial cells.
- V-g-c are present at extremely low density in the internodes of
myelinated axons = act pots do not occur in internodes.
= current generated by an action potential at one node of Ranvier
spreads electronically through the internode to the next node or
Ranvier.

Fig 5.19
- Current at node of Ranvier > threshold pot = triggers a new act pot
at this next node.

Saltatory conduction- “saltare”: leap or jump- act pot jumps from node to
node along the axon.

Myelin increases distance over which electronic current can spread by acting
as an insulator that prevents charge from leaking out across the membrane.

= saltatory conduction along a myelinated axon is much faster than

conduction along an unmyelinated axon of equivalent size.

Axons conduct action potentials unidirectionally Synaptic

transmission:
Electrically stimulate axon halfway along its length:
Conc. of Ca2+ inside
Axons will be generated (1) toward axon hillock (2) and toward axon terminal. the neuron is much
lower than conc.
Because depolarization caused by Na+ entering through Na+ channels spreads outside; eq. pot. for
in all directions along the axon, why do act pot only occur in downstream Ca2+= -70mV.
direction (axon terminal)

- Examine a natural act pot (axon hillock  axon terminal): the

region just upstream of the point you are observing must have
recently produced an act pot
o Result: Na+ channels in this upstream region of the axon
are in a conformation in w/c they are unable to open in
response to change in the membrane potential.
o Prevents backward (retrograde) conduction of act pot;
absolute refractory period also prevents summation of
act pots., bec a new act pot can only be triggered once
the ARP is completed.

Action potential frequency carries information

- By changing frequency rather than amplitude.

Resulting increased Ca2+ conc inside the axon terminal acts as a signal to
neurotransmitter containing synaptic vesicles.

SV- grouped into at least 2 distinct pools:

- Readily releasable pool of vesicles: located at active zone of the

synapse, bound to docking proteins called SNAREs. (exocytosis)
- Storage pool: vesicles bound to cytoskeleton.

Ca2+ that enters the synapse: binds to a protein (synaptotagmin) on the

membranes of vesicles in the active zone of the synapse.

= changes conformation of synaptotagmin, allowing to interact w SNARE

complex and synaptic membrane  exocytosis.

Postsynaptic cells- detect neurotransmitters using specific cell-surface

Ca2+ signals- causes vesicles from storage pool to move to active zone of
receptors.
plasma membrane and bind to docking proteins, ready for release following
subsequent act. pot.

Quantal release- pattern of release wherein the amount of

neurotransmitter a neuron releases increases in a step-like fashion, with
each step corresponding to the contents of a vesicle, rather than increasing
in a smoothly graded fashion as would happen if neurotransmitter were
released one mol at a time.

Action potential frequency influences neurotransmitter release

How is act pot frequency coupled to the extent of neurotransmitter

release?

Arrival of single act pot to at axon terminal  Ca2+ enters  bound up by

intracellular buffers or removed from the cytoplasm by Ca2+ ATPases 
keeps intracellular conc low and limiting the release of neurotransmitters.

High freq act pot: processes removing Ca2+ from the cell can’t keep up with
its influx and the intracellular Ca2+ conc increases  provides a stronger
signal for exocytosis.

Thus, the signal intensity that was coded by act pot freq. was translated into
differences in the amt. of neurotransmitter released by the neuron.

Acetylcholine is the primary neurotransmitter at the vertebrate

neuromuscular junction

ACh- biogenic amine synthesized from a compound called choline.

- occurs in the axon terminal in a reaction catalyzed by enzyme

choline acetyl transferase.
- AcetylCoA + choline  Ach + CoA
- Packaged into synaptic vesicle and stored until an action pot
arriving at the axon terminal triggers its releases  diffuses into
the synapse and binds to receptors on postsynaptic cell membrane.
Acetyl-CoA: from mitochondria
Signaling is terminated by acetylcholinesterase
Acetylcholinesterase- specific enzyme in neuromuscular junction
- Breaks Ach down into choline and acetate
- Reducing conc of Ach in the synapse causing the bound Ach to
release from the receptor.
- Plays an important role in regulating the strength of the signal to
the postsynaptic cell by regulating conc of neurotransmitter at the
synapse.
Nicotinic ACh receptors- receptor in skeletal muscle cells.
- Ability to bind to the drug nicotine
- Ligand-gated ion channels
- Contain non-selective channel that is permeable to Na+, K+, and
Ca2+
- Graded potentials in postsynaptic cell caused by these channels are
dominated by Na+ ions bec of its high driving force.
ACh binds to nicotinic rec.  rec changes shape  opening a pore in the
middle allowing ions to cross the membrane
Neurotransmitter amount and receptor activity influence signal strength
Neurotransmitter conc inc = postsynaptic cell response inc (up to the point
that all of the avail receptors are saturated).

Choline- taken up by presynaptic neuron and reused to form Ach
Acetate- diffuses out of the synaptic cleft.
Postsynaptic cells express specific receptors
Conc of neurotransmitter in synapse = balance bet rate of neurotrans release
from presynaptic cell and rate of removal of neurotrans from the synapse
Removal of neurotransmitter:
1. Can simply diffuse passively out of the synapse
 2. Surrounding cell, including presynaptic neurons, can also take up - Least common
neurotrans. type
3. Enzymes present in the synapse can degrade them.
Unipolar neuron (UN)-
Myasthenia gravis- example of a disease is an example of a disease state single process from the cell
caused by alterations in receptor number on muscle cells. body.

- Muscle weakness and inc susceptibility to muscle fatigue. - Splits into 2 main
- Autoimmune condition in which antibodies from a person’s branches
immune system destroy ACh receptors at neuromuscular junction.
- Symptoms can be treated by acetylcholinesterase inhibitors:
reduce the rate of removal of ACh from its receptos = inc conc of
ACh in the synapse.

Organophosphate pesticides, nerve gas sarin- acetylcholinesterase inhibitors.

o High doses of these agents inc the con of ACh in synapse = lead to
over excitation of muscles = twitching, muscle fatigue, paralysis,
death.

DIVERSITY OF NEURAL SIGNALING

Neuron functions:

(1) Receive and integrate incoming signals

(2) Conduct these signals through the cells
(3) Transmit signals to other cells

Structural Diversity of Neurons

Complexity of the neuron does not depend on the complexity of the animal
but on the function.
- Mammalian brain: many dendrites but may lack an obvious axon:
allows to integrate an enormous no of incoming signals from other
neurons.
- Muscle: longer axon bec it is specialized for rapid-long distance
electrical signaling.
Neurons can be classified based on their function
Sensory (afferent) neurons- convey sensory info from the body to CNS.
Interneurons- located within CNS and convey signals from one neuron to
another.
Motor (efferent) neurons- convey signals from CNS to effector organs.
(pseudounipolar)
- Sensory neurons that are involved in detecting environmental
signals and conveying this info to the rest of the NS.
Figure of neurons:
MN: receptors in dendrites and cell body detect incoming signals and
transduce then into an electrical signal in the form of a graded potential
- Incoming GP are conducted electronically to the axon hillock, which
acts as integrating center for the neuron.
- If the GP at axon hillock exceeds threshold pot, it triggers act pots
which are conducted along the axon to the axon terminal.
- Not all multipolar neurons generate act pot.
- In some with very short axons, electrotonic current spread is
sufficient to convey info along the axon.

- Skeletal muscles as well as smooth muscles and endocrine glands.
Neurons can be classified based on their structure
Multipolar neurons (MN)- have many cellular extensions (or processes) that
originate at the cell body.
BN: GP spreads to cell body, where it triggers act pot in 2nd process which acts
as an axon.
- Some do not use act pot to convey signals.
UN: their GP do not travel directly to the cell body

- Only one of these processes is an axon, whereas the remaining - Travel only as far as the beginning (initial segment) of the process
processes are dendrites. that leads to the cell body.
- Most common in vertebrates - If GP on this segment exceeds threshold pot, it will trigger act pot
 cell body  axon terminal
Bipolar neurons (BN)- have 2 main processes extending from the cell body, - Important point: integrating center is located in a very diff position
one of which is highly branched and conveys signal to the cell body in a UN compared to MN.
(functionally similar to dendrite)
- Invertebrates: more common.
- Other one conveys signal away from the cell body (axon)
- Retinal and olfactory cells
Cnidarians (sea anemones, jellyfish)- neurons lack polarity

- Capable of sending and receiving signals at either end and can

conduct signals in either direction along the neuron.

Neurons are associated with glial cells

Schwann cells- form myelin sheath; assoc. w motor neurons and many sensory
neurons.

- Increasing conduction speed of act pot along the axon

 - Essential for regeneration and regrowth of damaged sensory and
motor neurons.
- When neuron is damaged, they digest damaged axon and provide
a pathway for neuronal regrowth.
Oligodendrocytes- form myelin sheath for neurons in the NCS.
- May wrap around the axons of several neurons and thus, differs
from a Schwann cell which always enwraps a single neuron.
Astrocytes- large stellate (star shaped) cell bodies and many processes.
- Located in CNS; transport of nutrients to neurons, removal of
debris, guiding neuronal dev., and regulating contents of EC space
around neurons.
- In the brain often enwrap synapses and may play an imp role in
regulating synaptic communication by regulating neurotransmitter
levels.
- Form connections with each other and neurons via gap junctions.
- Actively communicate with each other through these using
intracellular Ca2+ and other signaling molecules.
Microglia- neuronal maintenance.
- Smallest glial cells.
- Similar to macrophages in immune system
- Remove debris and dead cells.
- Most active during trauma or a disease.
Ependymal cells- line the fluid-filled cavities of CNS.
- Cilia: to circulate cerebrospinal fluid
Satellite cells- specific type of glial cell that are found in the ganglia of the PNS
Enteric glia- assoc with the neurons of the gut.
- Functions similar to those of astrocytes in CNS.
Radial glia- found in CNS during development and play an important role in
structuring the developing NS.
o Maintain RMP but do not generate AP nor do they form obvious
chemical synapses.
o Although, they can take up neurotrans thus can regulate
neurotrans conc at the synapse.
o Gliotransmitters- released by astrocytes that can influence activity
of neurons and synapses.
- Glutamate, GABA, ATP
Gliocytes- invert glial cells.
- Functionally similar to astrocytes as they ensheathe synapses.
- Lack true myelin sheath but axons of peripheral neurons may still
be wrapped in several layers of glial celss membrane
- Proteins involved in the structure of myelin sheath of verts and
wrapping of inverts differ suggesting that molecular machinery
involved in invert wrappings is fundamentally diff from that of
myelin sheath of verts.
Diversity of Signal Conduction
- Electrotonically
- Combination of electrotonic current spread
- Regenerating action potential
- Shape of action potential and speed of conduction vary
Voltage-gated ion channels are encoded by multiple genes
Many ion channels exist as multiple isoforms: slightly different molecular
variants of the same protein, encoded by different genes:
Mammals: 18 separate genes encode v-g K+ channels and over 50 types have
been characterized among all animal species.
Voltage-gated K channels- cause the repolarizing phase of the action potential
in most neurons.
- Diverse isoforms result in diversity of shapes during repolarizing
phase of act pot in diff cells.
- Strong influence in excitability of the cell, act pot duration, and
frequency.
Example: K+ channels that open extremely quickly in response to
depolarization tend to make act pot more difficult to generate, bec K+ ions
leave the cell at the same time Na+ ions are entering, countering the depo due
to Na+ channels.
- Delayed rectifiers: respond relatively slowly to changes in
membrane pot, inc in length of the act pot.
Voltage-gated Na+ channels - less diverse
- 2 genes have identified in Drosophila and squid compared with 11
isoforms in mammals.
- Density has effect on the function of the neuron:
high density  lower threshold, more Na+ channels
are avail to open at a given stimulus intensity, more
Na+ will enter the cell.
= balance point bet dissipation and influx of Na+ ions
is more easily reached at a lower level of depo.
= smaller GP can already excite a neuron
high density  shorter relative refractory period
(bec of dec in threshold potential)
Voltage-gated Ca2+ channels can also be involved in
action potentials
- In neurons with these channels in their axon, these open at the
same time as (or instead of) Na+ channels.
- Ca2+ entry  depo (slower and more sustained than depo in Na+
influx)
- Important in establishing shape of act pot in excitable tissues other
than neurons: cardiac muscles
A sustained depo slows down the rate at which act pot can be generated by
prolonging refractory period.
 - Example: act pot that control rhythmic swimming in jellyfish have
sustained depo phase due to Ca2+ influx; last about 10x longer than
a typical vert act pot.
Conduction speed varies among speed
- Decreases with distance (conduction with decrement)
Why? Decrease in voltage is a direct result of the resistance of the material.
Resistance is cumulative with
distance.

Main strategies for inc speed of act pot conduction: An axon is not just a simple
conductor: consider more than
1. Myelination just IC and EC resistances:
2. Inc in diameter of axon- high conduction velocity have unusually
large-diameter axons: giant axons Most membranes contain K+ leak
channels, which unlike v-g-c, are
Cable properties of the axon influence current flow essentially always open. Thus, as
current travels along the axon,
The physical properties that govern the extent of current flow along an axon some + charge leaks out through
are similar to the physical principles governing the conduction of electrical these channels, dec current as it
current through transatlantic telephone cables. flows along axon.
Current- a measure of amount of charge moving past a point in a given amount Extent of + charge loss – depends
of time, and a function of the drop in voltage across the circuit and resistance on resistance
of the circuit.
high resistance  low
Ohm’s law- relationship bet current and voltage current flow across
membrane  less
V= IR
charge will be lost
I= current in Ampere; V= voltage drop across the circuit (measure of the energy
low resistance  high
carried by a unit of charge); R= resistance of the circuit.
current flow  more charge will be lost  greater dissipation of
- The difference in voltage bet 2 points is a measure of energy avail axonal current w distance.
to more charge from one point to the other, just as pot energy is a
Length constant (wavelength symbol)- effects of membrane
measure of energy avail to motor object from one point to another.
resistance, EC and IC resistance on distance an electrical signal can travel.
Resistance- measure of force opposing flow of electrical current.
- Distance over which a change in membrane pot will dec to 37% of
- Each compartment of axon has an assoc resistance, w/c impedes
its orig value.
flow of the current.
- When large, the change in membrane pot degrades less with
distance.
When small, change in mem pot degrades quickly with distance.
Small area of axon: 3 resistors: (1) EC fluid, (2) membrane, (3) cytoplasm. The
parallel bar symbol indicates the presence of a capacitor: device that can store
𝑟𝑚
electrical charge that consist of 2 conducting material separated by an 𝑙𝑒𝑛𝑔𝑡ℎ 𝑐𝑜𝑛𝑠𝑡𝑎𝑛𝑡 = √ ; m= membrane; i= IC; o= EC
(𝑟𝑖 + 𝑟𝑜 )
insulating layer.

Intra and extracellular fluid = conducting layers; phospholipids= ECr= usually assumed to be low and constant; often neglected in eq.
insulating layer
𝑟𝑚
𝑙𝑒𝑛𝑔𝑡ℎ 𝑐𝑜𝑛𝑠𝑡𝑎𝑛𝑡 = √
𝑟𝑖

Why does the length constant of membrane influence conduction speed

along axon?

Conduction along an axon represents a combination of electrotonic

conduction and act pot generation at specific point on axon.

Electrotonic conduction is very rapid compared w speed of opening and closing

channels during act pot.

A neuron that used only electrotonic current flow would transmit signals very
rapidly. (used in short axons)

In longer axons, act pot must be generated to boost signal before it dies out
bec of dec in voltage w distance. However, ability to signal over long distances
using act pot comes with a cause – reduced speed in signal conduction.

Bec electrotonic currents spread along axon extremely rapid, the farther a
threshold depo can spread along the axon, the shorter the length of time it will
take for an impulse to reach the end of the axon.

Intracellular and membrane resistance influence conduction speed inc the length constant of axon = inc speed of signal conduction along the
neuron by allowing signal to be carried farther by the more rapid electrotonic
Depolarization: inside  (+) charge; outside  (-) charged: electrotonic conduction rather than by repeated generation of act pot.
current spreads  depolarized adjacent regions of the membrane.

Change in membrane potential- measured as voltage drop across the

membrane Membrane capacitance influences the speed of conduction
Presence of membrane capacitor: when current is injected to a neuron= a
rectangular pulse of current does not result in an immediate change in
membrane potential of the cell.
o There is a lag caused by membrane capacitor.
o When the switch is closed, the voltage difference bet poles of
battery causes electrons to flow from cathode to anode. But
capacitor acts as an insulator, so (-) charges cannot flow across the
capacitor and pile up on one side.
Like charges repel and unlike charges attract.
Attraction which occurs across the thin insulating layer of the capacitor
- (-) charges on one side of the capacity pull (+) charges toward the
capacitor and repel (-) charges
= causing current flow through the circuit (electrostatic forces
acting across the insulating layer of the capacitor induce a current
in the circuit)
As more charges build up, they increasingly repel each other and it becomes
more difficult for additional charges to be deposited on the capacitor.
Eventually, the charge on the capacitor will equal the driving force coming
from the voltage drop across the battery and no more current will flow.
Capacitance- point when current stops flowing across a particular capacitor.
- Quantity of charge needed to create a pot diff bet 2 surfaces of the
capacitor.
- Depends on three features of capacitor:
(1) Material properties of the capacitor
(2) Area of 2 conducting surfaces
Larger area of capacitor  greater capacitance
(3) Thickness of insulating layer
Thicker insulating layer  lower capacitance
High capacitance capacitor store large amounts of charge
low capacitance  only able to store small amounts of charge
Why is the membrane capacitor important for the function of axon?
When you introduce an elec current into an axon (open Na+ channel), the
membrane voltage will change, but more slowly than expected because
initially most of the current flows into the membrane capacitor.
As capacitor becomes fully charged, it becomes more difficult for current to
flow into capacitor and once the membrane capacitor is charged, current will
not flow into this portion at all.
At this point, current will begin to flow through the resistor, changing
membrane pot.
= there is a balance bet current flowing through membrane resistors and
current flowing into membrane capacitors.
Time constant (Ί)- time needed for the membrane capacitor to charge.
- Defined as the time taken for the membrane pot to decay to 37%
of its orig value (or reach 63 % of its maximal value)
- Larger: longer it will take for the membrane to reach given mem
pot.
Ί = 𝒓𝒎 + 𝒄𝒎 ; r = membrane resistance, c= membrane capacitance
(inc in both will inc time capacitance = delaying current flow)
- Has important consequences for temporal summation in neuronal
cell bodies.
TIME CONSTANT IN TEMPORAL SUMMATION
Imagine 2 GP occurring at the same time in presynaptic cell that sum to provide
a suprathreshold potential.
What will happen if these 2 GP occur at diff time?
If TC is small = these potentials will decay rapidly and less likely to
sum to provide suprathreshold pot.
If TC is large = will decay slowly; more likely to overlap in time =
sum to a suprathreshold pot.
TIME CONSTANT ON CONDUCTION SPEED
As current spread electrotonically, some of the voltage must first be used in
order to charge the membrane capacitor.
Only once the capacitor is fully charged does current begin to flow across the
membrane and alter membrane pot.
= electrotonic current spread is delayed.
Smaller time constant  faster the membrane an depolarize by a given
amount and greater rate of electrotonic current spread and act pot
propagation.
Three main factors affect speed of act pot propagation:
1. Kinetics of v-g-channels
Example: act pots propagate faster at high temp bec channels open
faster at warmer temp
2. Increased speed or distance of electrotonic current spread
3. Length constant and time constant
Giant axons have high conduction speed
- Absent in mammals
- Easily visible to the naked eye, mm in diameter larger than
mammalian axons (> 5um)
- Involved in signaling to the mantle cavity so that it contracts and
allows squid to use jet propulsion to swim.
- conduct signals more rapidly as justified in the effects of
membrane resistance and IC resistance on length constant of
membrane.
LC inc as MR inc ; LC dec as IC inc
Membrane resistance- inversely prop to the surface area of membrane.
- As SA inc, so does no of leak channels = greater ion flow across
membrane = membrane resistance dec.
SA= 2𝜋𝑟ℎ
r = radius of axon, h= length
Membrane pot is inversely prop to radius of the axon:
- Radius and diameter inc = membrane resistance dec.
𝑉𝑜𝑙𝑢𝑚𝑒 = 𝜋𝑟 2 ℎ
- Vol inc = IC resistance dec
- IC resistance decreases in prop to radius of axon squared.
MEMBRANE RESISTANCE AND IC RESISTANCE ON LENGTH CONSTANT OF
MEMBRANE
Axon radius inc = membrane resistance and IC restance dec
o IC resistance dec in prop to radius of axon squared while membrane
resistance dec in direct prop to the radius of the axon.
o Inc radius has greater effect on IC resistance than membrane
resistance.
The net effect of inc the radius is to increase the speed of conduction.
 o Membrane capacitance inc with membrane area = effects of
membrane resistance and membrane capacitance on the time
constant tend to cancel each other out.
= changes in time constant have small effect on local
current flow as axon diameter increases.
Myelinated neurons evolved in the vertebrates
Disadvantages of large axons:
1. Takes up space= may limit no of neurons that can be packed into
NS.
2. Have larger volumes of cytoplasm per unit length, making them
energetically expensive to produce and maintain.
High density of voltage-gated channels at the nodes of Ranvier is also imp in
the conduction of signals in myelinated neurons
High density of channels decreases the threshold potential for firing act pot in
this region = decreasing the size of electrotonic current needed to trigger an
act pot
Diversity of Synaptic Transmission
- Some neurons do not release neurotransmitters onto their target
cells
 Electrical synapses utilize gap junctions that directly connect them to their
target cells

= vertebrates developed myelinated axons to speed up conduction - Composed of a series of proteins that form small pores in the
membranes of two adjacent cells, allowing ions and other
- Except lampreys and hagfish molecules to travel directly from cell to cell.

Myelination increases conduction speed
Myelinated neurons conduct signals more rapidly > unmyelinated neurons
- greater proportion of the signal conduction occurs electrotonically
= w/c is much faster than generating action potential
 Chemical synapses: the presynaptic neuron converts its electrical signal to
a chemical signal in the form of one or more neurotransmitters, which diffuses
across the synapse to the postsynaptic cell and binds to receptors.
Electrical and chemical synapses play different roles

Myelin sheath inc the length over w/c electrotonic current can spread
before it drops below the threshold potential required to generate an
action pot at the next node of Ranvier

Myelin sheath acts as insulation for axon, reducing current loss through
leak channels and inc membrane resistance

Reduced ion leakage = inc length constant of mem

= inc distance that local current can travel

electrotonically before degrading

= inc overall conduction velocity

Transmission across a chemical
Presence of myelin sheath = decrease capacitance synapse
Relatively slow compared with the
- bc capacitance is inversely proportional to the thickness of the speed of propagation of an action
insulating layer in the capacitor potential bec of the need for
docking and fusion of synaptic,
diffusion across synapse and signal
Many layers of cell mem of myelin sheath act together as single insulator transduction in postsynaptic cell.
Transmission across electrical
synapse
Instantaneous bec it occurs via
electrotonic current spread and
thus is not associated with any
significant synaptic delay.

- Thus, although each mem alone has same thickness, the effective Associated with synaptic delay of Easily convey information in either
thickness of many layered myelin sheath is much greater several milliseconds direction, bec electrical current or
ions can move freely in either
direction through gap junctions.
Increase in thickness of mem

= dec the capacitance The signal is not necessarily the The signal in postsynaptic cell is
same as in presynaptic cell. always similar to signal from
= dec time constant of membrane presynaptic cell.
Provides additional level of Direct electrical coupling across this
= inc speed of electrotonic conduction in internodes regulation for the nervous system limit the diversity of signal in
(neurotransmitters). postsynaptic cell.
Complex neural pathways Simple nervous system: cnidarians
(jellyfish, sea anemones)
Placement of node of Ranvier is critical for the function of myelinated axons
Also plays a role in complex NS:
- Nodes cant be places too far apart or the signal will not be sufficient mammalian brain- synchronizing
to depo the neuron beyond threshold at the next node brain function (hormone-secreting
 bc current inevitability decrease w/ distance cells of hypothalamus connected by
 although less so in a myelinated axon than in an unmyelinated electrical synapses).

Length of internodes is about 100x the diameter of the axon, ranging from
about 200 um – 2 mm

- electrotonic spread can carry a suprathreshold depo past several

nodes of Ranvier, w/c then appear to fire simultaneously
Chemical synapses have diverse structures - Vesicles containing peptide neurotransmitters are then
transported from cell body to the axon terminal along a complex
network of microtubules via fast axonal transport.
- Snails: synthesize peptide neurotrans in both axon and axon
terminal.

Purines- do not fit into any simple chemical class.

- ATP, important in energy metabolism

Axon terminal- swelling in the terminal branches of a split motor neuron.
(terminal bouton or synaptic knob)
- NO gas, not packaged into vesicles: diffuse freely out of presynaptic
neuron in all directions into every nearby cell = cannot be stored
and must be synthesized only when/as needed.
Neurotransmitters can be excitatory or inhibitory

- Some axons form synapses at axon varicosities or swellings along A. Inhibitory neurotransmitter
the axon that can be arranged like beads on a string.  cause hyperpolarization, making the postsynaptic cell
- Autonomic neurons: form synapses with their effector organs. less likely to generate an act pot.
Neuroeffector junctions: differ from true synapses in that the  Causes a change in membrane pot known as inhibitory
postsynaptic cell membrane at the junction is not specialized and postsynaptic potentials (IPSPs)
does not contain a high conc of receptors.
: neurotransmitters diffuse broadly and contacts B. Excitatory neurotransmitter
receptors located across large areas of target organ.  cause depolarization
 Causes excitatory postsynaptic potentials (EPSPs)
En passant synapse- similar type of synapse that consists of a swelling along
the axon of the presynaptic neuron.

- Differ in neuroeffector junctions in that postsynaptic membrane

may be specialized and contain high densities of receptors.

Spine synapse- the presynaptic cell connects with a specialized structure,

dendritic spine, on the dendrite of postsynaptic cell.

Neuron-to-neuron synapses

1. Axodendritic synapse- form bet axon terminal of a neuron and

dendrite of another
2. Axosomatic synapse- bet axon terminal of a neuron and cell body
of another.
3. Dendrodendritic synapse- bet dendrites of 2 neurons and are
often electrical synapses that allow communication of info in
both directions bet neurons.
4. Axoaxonic synapse- axon terminal of presynaptic neuron and
axon of a postsynaptic neuron; most often found at axon hillock
or axon terminal of postsynaptic neuron.

Types of neurotransmitters

- Must be synthesized in neurons

- Must be released at presynaptic cell membrane following
depolarization
- Must bind to postsynaptic receptor and can cause a detectable Neurotransmitter receptors can be ionotropic or metabotropic
effect.
- Grouped into amino acids, neuropeptides (neuroactive peptides), Ionotropic receptors- ligand-gated ion channels.
biogenic amines, acetylcholine and a grab-bag class consisting of - Conformation changes of the protein is caused by neurotransmitter
neurotransmitters that do not fit into any of the other groups. or chemical signaling molecule binding.
- Initiate rapid changes in mem pot
Amino acids
1. Glycine
2. Aspartate
3. Glutamate
4. Gamma-aminobutyric acid (GABA)- derivative of glutamate.

Neuropeptides- short chains of AA synthesized in RER (found in cell body)

 - Example: nicotinic ACh receptors
Metabotropic receptor- change in conformation of the receptor that sends
signal via 2nd messenger, initiating a signaling cascade within the postsynaptic
cell.
- A signaling cascade activated by this ultimately sends a message to
ion channel proteins, modulating activity of ion channels on
postsynaptic cell membrane = altering mem pot.
- G-coupled receptors
- Cause slower-acting changes bec of the complex signaling
pathways bet binding of neurotrans and opeing of ion channels
- Often cause long term changes by affecting the transcription or
translation receptors and ion channels.αα
Acetylcholine receptors can be ionotropic and metabotropic
Cholinergic receptors- classified into:
1. Nicotinic- ionotropic receptors that cause rapid response in the target cell.
- made up of α, β, γ, δ and ε encoded by diff isoforms.
- First studied in electric organ of Torpedo californica.
- Its subunits are arranged like the staves of a barrel around a central pore.
Nicotinic receptors of ANS- made up of α3, α5, α7, β2 and β4 subunits while
receptors in brain are predominantly α4 and β2 subunits.
2. Muscarinic- metabotropic receptors that causes slow response and
indirectly coupled to ion channels through G proteins.
- Drug muscarine binds to them and not to nicotinic receptors
- Found in brain, heart, gut, bronchial passage
The biogenic amines play diverse physiological roles
 Synthesized in axon terminal using amino acid as a precursor
 Acetylcholine: can be considered one but is classified separately
bec it isn’t synthesized from an amino acid precursor and the amino
grp in in the center of the mol rather than at one end.
Catecholamines- dopamine, norepinephrine, epinephrine
- Synthesized via common pathway from tyrosine
- Epi and nore: play a role in PNS and are involved in regulating
physio processes including heart rate and breathing.
: receptors are called adrenergic receptors (adrenaline). Both bind
to α receptors although epi binding is weak.
Opposing effects:
 norepi binds to β2 receptors on smooth muscle surrounding
bronchioles, the muscle relaxes.
= inc diameter of bronchioles
 norepi binds to α1-adrenergic receptor, the muscle contract. = dec
diameter
= inc blood pressure
Serotonin- synthesized via common pathway from tryptophan with hormone
melatonin.
Figure 5.37
Binding of NE to α1-adrenergic receptor → signal transduction (Gq)
→ activates Phospholipase C → breaks down
phosphatidyl (PIP) into → diacylglycerol triphosphate (IP3)
Activation of α1-adrenergic receptor causes smooth muscle surrounding bv
leading to skin and internal organs to contract➔ vasoconstriction.
In these smooth muscles:
DAG activates→PKC→phosphorylates and activates Ca2+ channels
→allowing Ca2+ ions to enter from EC space
IP3 binds to Ca2+ channels on sarcoplasmic reticulum→release of Ca2+ from
intracellular stores→combine w ions from EC→ vasoconstriction.
Cont. of α2 receptor in table 6:
Activates G protein (Gi) inhibitory G protein→inactivates adenylate
cyclase→inhibits cAMP
Decrease cAMP production→inactivates PKA→Ca2+ channels are no longer
being phosphorylated→difficult to open.
- NE acts as negative feedback signal inhibiting its own release.
Cont. of β1 adrenergic receptor in table 6:
Binding activates Gs (stimulatory protein) → activates adenylate cyclase
→ inc cAMP → activates PKA → phosphorylation
Cont. of β2 adrenergic receptor in table 6:
- Smooth muscles = surrounding BVs leading to skeletal muscles and
smooth muscle of bronchioles.
cAMP formed inhibits myosin light chain kinase→muscle relaxation →dilation
of bronchial passages→inc blood flow to skeletal muscle
NE and EPI: response to stressful stimuli
Neurons can synthesize more than one kind of neurotransmitter
Different neurotransmitters appear to be released from a single axon terminal
at different stimulus frequencies.
- Example: low frequency stimulation releases ACh High freq
stimulation release neuropeptide.
Likely that diff vesicles reside in a single neuron containing diff
neurotransmitters.
Neurotransmitter release varies depending on physiological state
Synaptic plasticity- ability of a synapse to change its function in response to
patterns of use, underlies many imp brain functions, learning and memory.
Synaptic facilitation- inc in neurotrans release in response to repeated act pot.
- OccursbectheaccumulationofintracellularCa2+ following each
action pot allows more neurotrans to be released by subseq act
pot.
Synaptic depression- dec in neurotrans release w repeated act pot, occurs bec
of the progressive depletion of the readily accessible pool of synaptic vesicles
that is avail for fusion and exocytosis.
Post-tetanic potentiation (PTP)- occurs after a train of high freq act pot in
presynaptic neuron.
- Differ from those involved in synaptic facilitation and are thought
to involve a Ca2+-dependent inc in the avail pool of neurotrans
containing vesicles.
Evolution of Neural Signaling
Many organisms use electrical signal
Plants- do not have specialized tissue for conduction action potentials to
specific locations over long distances
- Green algae produce act pot for signaling communication.
- Appears to propagate act pot through its tissues: xylem and
phloem
- Venus fly trap (Dionaea muscipula) & sensitive plant (Mimosa
pudica): use act pot to coordinate the movement of specialized
structures that they use to trap insects.
- Algae (Chara corallina_: giant cells capable of generating act pot;
coordinate cytoplasmic streaming.
Action potentials in nonmetazoans involve Ca2+
Chara- act pot resulting from ion movements through Cl- channels that are
activated in a Ca2+-dependent manner.
 - influx of Ca2+ and efflux of Cl- depolarizes the cell.
 - Acts in an all-or-none fashion but conducted about 1000x more
slowly than typical vert act pot.
Paramecium- ciliate protist, swims via coordinated beating of the cilia that
cover its exterior.
 - If it makes contact w a solid object, it will back up by reversing.
 - This reversal is a result of opening Ca2+ channel w/c causes act
pot.
Actinocoryne contractilis- both Ca2+ and Na+- dependent act pot. Animals
have unique voltage-gated Na+ channels
All metazoans have at least one gene that codes for a Na+ channel.
- Recently discovered in bacteria
Neurotransmitters evolved from ancient signaling molecules
Jellyfish- have mechanisms of Ca2+- induced neurotrans release from
presynaptic neurons very similar to mechanisms used by mammalian neurons
Choanoflagellates- sister group of metazoans share even more of these genes.
- Suggest that synaptic transmission arose as a modification of
mechanism for cell-to-cell comm present in many organisms.
Ach has been observed in bacteria, algae, protozoan and plants (organisms w
no NS).
Lancelet/ Amphioxus- one catecholamine-receptor gene, and uses dopamine
not norepinephrine as a neurotransmitter.
Mammals- 5 dopamine receptors, 9 alpha adrenergic receptors, 3 beta-
adrenergic receptors.