 CNS: brain and spinal cord

 Peripheral nervous system

 Afferent system: senses to the brain
 Somatic senses: skin, muscles, and joints
 Special senses: Taste, vision, hearing, equilibrium (car sickness, vertigo), smell
 Visceral senses: internal environment (fullness of stomach, blood pressure, pH)
 Efferent: CNS to periphery
 Somatic: skeletal muscle
 Autonomic: sympathetic and parasympathetic
 Sympathetic: cardiac muscle, smooth muscle, glands, internal organs,
digestive system
 Parasympathetic: enteric nervous system

Cell Types
 Neurons: excitable cells that can transmit electric signals (action potentials)
 Dendrites: receive synaptic signals at synapses
 Axon: nerve fiber, starts at cell body in the region called the axon hillock
 1 mm to 1 m in length
 Axon terminals: contain synapses and where you're signaling to other cells
 Glial cells: provide structural and metabolic support, 90% of the cells in nervous system,
involved in myelination
Axonal Transport
 Enzymes are required for synthesizing neurotransmitters at the axon terminal and for
exocytosis
 Enzymes are produced in the cell body
 Simple diffusion would take days for the enzymes to reach the terminals
 Anterograde transport: from soma to axon
 Retrograde transport: from axon terminals to soma. Returns vesicles/organelles to soma
for degradation
  Slow transport: small soluble molecules in the cytosol, vesicles, organelles, cytoplasmic
proteins, cytoskeletal structures
 0.5-40 mm/day
 Fast transport: transport of membrane bound vesicles, synaptic vesicles
 100-400 mm/day
 Hydrolysis of ATP causes protein to walk
 Kinesin: anterograde
 Dynein: retrograde

Structural classification of neurons

 # of processes projecting from the soma
 Bipolar neurons: 2 processes extending from the cell body: the dendrite and the
axon
 Typically sensory neurons
 Pseudo-unipolar: subdivision of bipolar neuron, looks like a single projection from
the cell body that's all connected. The dendrite is a specialized dendrite that
behaves like a peripheral axon. Connects to sensory receptors where as the central
axon connects to the CNS
 Multipolar: multiple projections off of the cell body most of which are dendrites and
an axon
 Functional properties
 Efferent neurons
 Motor neurons that extend to skeletal muscle and the neurons of the
autonomic nervous system
 Afferent neurons
 Transmit info from either sensory receptors visceral receptors
 Most afferent neurons are pseudo-unipolar neurons with the cell body
located outside the CNS in a ganglion. Peripheral axon is in the peripheral
organ and the cetnral axon terminates in the CNS where it releases
neurotransmitter to communicate with other neurons
 Interneurons: receive signals form periphery and sending signals out to the
periphery, found only in the CNS
Organization of neurons
 Neurons with similar function are grouped together
 Aligned so that soma, dendrites, and axons are grouped together
 CNS
 Groups of somata: nucleus (pl. nuclei)
 Groups of axons: pathway/tract/commisure
 PNS
 Group of somata: ganglion (ganglia)
 Group of axons: nerve
Glial Cells
 90% of cells in the nervous sytem
 Provide structural & chemical support to neurons
 Astrocytes, Microglia, Oligodendrocytes, Schwann cells
Myelin Sheath
 Found in jawed vertebrates
 Layers of plasma membrane from support cells
  Lower protein than other plasma membranes
 Channel and carrier proteins absent
 Insulates neurons
 Serves to increase speed of action potential
 Schwann cell: PNS, one schwann cell forms one myelin sheath, myelinates one section of
an axon
 Oligodendrocytes: one forms several myelin sheaths, myelinates sections of several axons
 Myelin sheath reduces the leakage of ions across the cell membrane
 Nodes of ranvier: axonal membrane contains voltage gated sodium and potassium
channels

Establishment of the Resting Membrane Potentials

 Voltage: the measure of potential energy generated by separation in charge (mV)
 Measured b/w two points
 In cells, called membrane potential (Vm)
 Current: the flow of electrical charge form one point to another
 Used to do work
 Resistance: the hindrance to current
 Insulators have high resistance
 Conductors have low resistance
 Ohms Law: describes relationship b/w voltage, current, and resistance
 I= E/R
 I:current, E:voltage, R:resistance
Membrane Potentials
 The body is electrically neutral but there are regions where on type of charge
predominates
 Inside and outside of a cell separated by membrane
 Energy is required to maintain the difference in charge
 Coming together of charge releases energy (separation has potential energy)
 Membrane potentials are described as the potential inside the cell relative to the outside
 Two factors critical in determining resting membrane potential
 Ion concentration gradients
 Membrane permeability to these ions

Neuronal Ion Channels

 Leak channels (nongated): always open
 throughout the plasma membrane
 maintain resting membrane potential
 Ligand-gated channels: open/close in response to ligand binding,
 dendrites and cell body, areas that receive communication from presynaptic
neurons
 involved with synaptic potentials
 Ex: acetylcholine channel
 Voltage-gated channels: open/close in response to changes in membrane potential
 Sodium & potassium ion channels: throughout, but most concentrated in the axon
hillock
 Initiate and propagate action potentials
 Calcium ion channels
  Most concentrated in the axon terminal
 Release neurotransmitters

Resting Membrane Potential

 The Na+/K+-ATPase pump creates & maintains concentration gradients
 Na+: more concentrated outside of cell (inward chemical driving force)
 –K+: more concentrated inside of cell (outward chemical driving force)
 20% of the resting membrane potential directly due to this pump
 3Na+ out, 2K+ in, net 1+ out
 80% of resting membrane potential indirectly due to this pump (ion concentration
gradients)
 K+ contribution (hypothetical cell)
 Starting Vm= 0mV
 Na+ is balanced by Cl-
 K+ is balanced by A-
 Sodium ions are at a higher concentration outside the cell and potassium are
concentrated inside the cell
 Membrane is permeable to K+, chemical driving force pushes K+ out of the cell
 Chemical force is constant
 As more K+ diffuses out of the cell, the inside of the cell becomes more negative
 Electrical driving force acts to pull K+ back into the cell
 Electrical force changes as the potassium ions move across the membrane
 Initially, the chemical force is greater than the electrical force bc the membrane
potential is small so potassium ions move out of the cell. As more potassium ions
leave the cell, the membrane potential becomes greater and electrical force pulls
potassium back into the cell
 K+ in the cell eventually reaches equilibrium potential. (-94 mV)
 Chemical & electrical forces opposite in direction, equal in magnitude, net
electrochemical force=0

 Na+ contribution
 Starting Vm=0 mV
 Membrane is only permeable to Na+
 Chemical driving force pushes Na+ into the cell
 As Na+ diffuses into the cell, the cell becomes positive and the electrical driving
force acts to push Na+ out of the cell
 Eventually reaches equilibrium (+60 mV)
 The actual equilibrium potential for sodium varies based on the concentration
gradient for sodium ions across a given neuron

 Neurons are 25x more permeable to K+

 Ion distribution
 Outside cell: Na+ and Cl-
  Inside cell: K+ and organic anions
 Membrane is more permeable to K+ so more K+ leaves the cell than Na+ enters and
the inside of the cell becomes negative.
 Electrical forces develop
 Na+ into cell
 K+ back into cell
 Due to electrical forces
 K+ outflow slows
 Na+ inflow speeds
 Membrane potential stabilizes at -70mV
 Steady state: requires energy
 Na+/K+-ATPase pump maintains resting potential
 The resting membrane potential is closer to K+ equilibrium potential (-94 mV)

In a neuron at rest, neither ion is at equilibrium. Electrochemical forces are acting on both ions,
causing sodium to continually leak into the cell and potassium out the cell. This slowly alters the
ion concentrations inside the cell, raising the sodium concentration while lowering the
potassium concentration. So Na/K pump actively transports sodium out of the cell and
potassium into the cell using ATP for energy.

Forces Acting on Ions

 If the membrane potential is not at equilibrium for an ion:
 The electrochemical force is not 0
 The net force moves the ion across the membrane in the direction that favors
equilibrium
 The strength of the net force increases the farther away the membrane potential is
from the equilibrium potential
 K+
 Ek=-94 mV
 Electrical force: into the cell (weaker)
 Chemical force: out of the cell (stronger)
 Net force is weak: K+ flows out of the cell, but the membrane is highly permeable to
K+
 Na+
 Ena= +60mV
 Electrical force is into the cell
 Chemical force is into the cell
 Net force is strong: Na+ flows into the cell, but the membrane has low permeability
to Na+

Quantifying Resting Membrane Potential

 Nernst equation can't calculate the membrane potential of a cell. It only takes into
consideration the equilibrium potential of one type of ion.
 Goldman-Hodgkin-Katz: calculates the resting membrane potential with multiple ions.
Ions with permeability of 0 aren't included in the equation.
 

Quantifying Ion Current

 Current: the movement of ions across the membrane
 I=current, g=conductance (related to permeability), Vm, E=equilibrium potential for ion
 Ina=Gna(Vm-Ena)
 Ik=Gk(Vm-Ek)
 Sodium & potassium channels responsible for the resting membrane potential are leak
channels which are always open

Electrical Signaling Through Changes in Membrane Potential

 Electrical signaling occurs through changes in membrane potential
 Gated ion channels
 Open/close in response to stimuli
 Ion movement=electrical signal
 Types of gated channels
 Voltage gated
 Ligand (chemically) gated
 Mechanically gated: in response to mechanical force. Channels are found associated
with sensory or visceral receptors located at the end of afferent neurons
 Types of electrical signals
 Graded potentials: smaller, communicate over short distances
 Initiated by a stimulus: (chemical) neurotransmitter binding or sensory stimuli
 Small change in membrane potential
 Magnitude varies depending on strength of stimulus
 Spread by electrotonic conduction
 Graded potential creates charge separation within the intracellular fluid
and within the extracellular fluid, which generates currents in these
fluids. These currents travel to adjacent areas of the cell membrane,
causing voltage changes. This voltage spread.
 Are decremental: magnitude decays as it spreads
 Threshold
 Graded potentials determine whether an action potential will occur
 Excitatory: depolarization: closer to threshold
 Hyperpolarization: further from threshold
 Temporal summation: same stimulus, repeated close in time
 Spatial summation: different stimuli, overlap in time
 Summation of hyperpolarizing and depolarizing graded potentials cancel each
other
 Action potentials: larger, communicate over long distances
 Rapid, large depolarization used for communication
 Occurs once threshold is crossed
 At the membranes of excitable tissue (nerve or muscle)
 Can travel long distances
 Alan hodgkin & andrew huxley
 Resting membrane potential: Pk> Pna
  Membrane potential close to Ek, far from Ena
 Depolarization: graded potentials bring membrane to threshold, crossing the
threshold triggers the opening of Na+ channels, slow closing of Na+ channels,
slow opening of K+ channels
 The opening of K+ channels and the closing of Na+ channels is the
reason that the action potential does not reach Ena
 Goes from -70 mV to +30 mV
 Repolarization: Na+ channels closed, K+ channels opened
 After hyper-polarization: K+ channels remain open beyond the resting
membrane potential. Membrane potential gets close to Ek. Na+/K+ ATPase
restores the resting membrane potential
 Voltage-Gated Channels
 Two gates are associated with the channel
 Activation gate (positive feedback system) & inactivation gate
 Activation gates: opening of sodium channels during depolarization
 Inactivation gates: closing of sodium channels during repolarization
 For a sodium channel to be open, both gates must be open
 3 conformations: closed but capable of opening (inactivation gate is open),
open (both are open), closed and incapable of opening (inactivation gate is
closed)
 Regenerative mechanism: opening of some sodium activation gates causes
more sodium activation gates to open by regenerating the stimulus to open
the gates, which is depolarization
 Voltage-gated K+ channels: one gate, depends on voltage and time, negative
feedback system
 As the cell repolarizes, the depolarizing stimulus weakens & potassium
channels slowly close
All or none principle: the level of depolarization reached at the peak depends not on the
strength of the stimulus but rather on the relative strengths of the electrochemical gradients for
sodium and potassium ions & the relative permeabiliteis of the membrane to these ions

Action Potentials: Refractory Period

 Period of time following an action potential, marked by decreased excitability
 Absolute: spans all of depolarization & most of repolarization phase. 2nd action potential
can't be generated. Na+ gates are inactivated.
 Action potentials cannot sum because the absolute refractory period prevents an
overlap of action potentials
 Relative: spans the last part of the repolarization phase and hyperpolarization. 2nd action
potential can be generated with a stronger stimulus. Some Na+ gates are closed; some are
inactivated.
 Consequences of refractory period: all or none principle, frequency coding, unidirectional
propagation of action potentials
Factors affecting propagation
 Refractory period: unidirectional
 Axon diameter
 Larger: less resistance, faster
 Smaller: more resistance, slower
 Myelination
 Saltatory conduction
 Faster propagation