Nerves and Communication

Who Are They What brings them together?

S. Mukherji, IIT-Bombay (mukherji@iitb.ac.in)

Who Are They What brings them together?

Amyotrophic Lateral Sclerosis (ALS) aka Lou
Gehrig's disease.
Muscle weakness and atrophy throughout the body
due to the degeneration of the upper and lower
motor neurons
Parkinson's disease aka paralysis
agitans) is a degenerative disorder
of the central nervous system.
death of dopamine-generating
cells in the substantia nigra,
most obvious symptoms
are movement-related ..
.. thinking and behavioral problems
may arise

Alzheimer's disease (AD) is the most

common form of dementia.
Early stages, the most common
symptom is difficulty in remembering
recent events. Later confusion,
irritability, aggression, mood swings,
trouble with language, and long-term
memory loss. Even later bodily functions
are lost, ultimately leading to death

S. Mukherji, IIT-Bombay (mukherji@iitb.ac.in)

Muscle cells and Nerve cells - Specialists

The muscle cell has made contraction its specialty.

Its cytoplasm is packed with organized arrays of
protein filaments, including vast numbers of actin
filaments and mitochondria.
The nerve cell stimulates the muscle to contract,
conveying an excitatory signal to the muscle from
the brain or spinal cord.
Schwann cells are specialists in the mass production
of plasma membrane, which they wrap around the
elongated portion of the nerve cell, laying down
layer upon layer of membrane like a roll of tape, to
form a myelin sheath that serves as insulation.

S. Mukherji, IIT-Bombay (mukherji@iitb.ac.in)

Features of the Nerve Cell

The nerve cell has to be extraordinarily elongated

o
o

After all it is carrying a signal from the brain to a far off muscle.
The main body, containing the nucleus, may lie a meter or more
from the junction with the muscle.

The cytoskeleton has to be well developed so as to

maintain the unusual shape of the cell and to transport
materials efficiently from one end of the cell to the other.
The plasma membrane, which contains proteins that act
as ion pumps and ion channels, causing a movement of
ions that is equivalent to a flow of electricity.

All cells contain such pumps and channels in their plasma

membranes, however the nerve cell has exploited them in such a
way that a pulse of electricity can propagate in a fraction of a
second from one end of the cell to the other, conveying a signal
for action.
S. Mukherji, IIT-Bombay (mukherji@iitb.ac.in)

Membrane proteins in the lipid bilayer

Ref. Quantitative Human Physiology by Joseph Feher

S. Mukherji, IIT-Bombay (mukherji@iitb.ac.in)

Ionophores and Voltage/Ligand Gated Channels

Ref. Quantitative Human Physiology by Joseph Feher

S. Mukherji, IIT-Bombay (mukherji@iitb.ac.in)

Concentrations of Na, K and Ca and resting

membrane potential across muscle cell membrane

Ref. Quantitative Human Physiology by Joseph Feher

S. Mukherji, IIT-Bombay (mukherji@iitb.ac.in)

The Nernst Equation

The Equilibrium Potential across a membrane arises from the balance between
electrical forces and mechanical (i.e. diffusion) forces.
We can derive it either from the Ficks laws of diffusion or from the energetics
point of view.
x
x
0
x ,i

x ,i

0
0
x ,i

RT ln C x ,i

zx

x ,i

0
x ,o

RT ln C x ,o

zx

x ,o

0
x ,o

x ,o

RT C x ,o
ln
z
C x ,i

For sodium ions at 37 C this translates

to 61.5 mV per decade gradient.

S. Mukherji, IIT-Bombay (mukherji@iitb.ac.in)

What if there are multiple ions

Nernst-Planck Electrodiffusion Equation

Ii

From Ficks Law with

an electrical force

z Ji

Ci Di
z Di
Ci z i
x RT
x
Integrating over the thickness of the membrane
from x 0 to gives

I ion

D z2 2
E m Ci C o e
RT
1 e

z
Em
RT

z
Em
RT

Goldman-Hodgkin-Katz current
equation

We can derive the voltage

equation from this

S. Mukherji, IIT-Bombay (mukherji@iitb.ac.in)

Goldman-Hodgkin-Katz Equation

Earlier we assumed a hypothetical membrane through which only one

type of ion can pass through but life is not so simple..
o
o

Many other ions are also present and some of them may also pass
Membrane permeability to ions may be time varying.

An outcome of integrating the Nernst-Planck Electrodiffusion

Equation gives the Goldman-Hodgkin-Katz Equation

Em

RT

PK [K ]o PNa [ Na ]o PCl [Cl ]i

ln
PK [K ]i PNa [ Na ]i PCl [Cl ]o

S. Mukherji, IIT-Bombay (mukherji@iitb.ac.in)

Equilibrium potentials for Na, K, and Cl in a

muscle cell

Ref. Quantitative Human Physiology by Joseph Feher

S. Mukherji, IIT-Bombay (mukherji@iitb.ac.in)

Conductances to Ions

The GHK current equation describes current carried by any ion, given
its concentration on two sides of a membrane and the membrane
potential.
At the equilibrium potential for each ion there is no current due to
that ion (reversal potential).
Following Ohms law and noting that the reversal potential is nonzero we can say that for chord conductance gi :

gi

Ii
E

Ii
Em

Ei

Similarly the slope conductance g is :

dI i
dEm

S. Mukherji, IIT-Bombay (mukherji@iitb.ac.in)

Currents carried by K+(left) and Na+ (right) as predicted by the

GHK current equation if the membrane were permeable only to
K+ or to Na+

Ref. Quantitative Human Physiology by Joseph Feher

S. Mukherji, IIT-Bombay (mukherji@iitb.ac.in)

Balance of forces driving Na+ movement

Ref. Quantitative Human Physiology by Joseph Feher

S. Mukherji, IIT-Bombay (mukherji@iitb.ac.in)

Transduction and Transmission of Stimulii

Ref. Quantitative Human Physiology by Joseph Feher

S. Mukherji, IIT-Bombay (mukherji@iitb.ac.in)

Measuring the Membrane Potential and Stimulating it

Ref. Quantitative Human Physiology by Joseph Feher

S. Mukherji, IIT-Bombay (mukherji@iitb.ac.in)

Effect of Hyperpolarizing and Depolarizing stimulii of varying

intensity on the axon membrane potential, Em

S. Mukherji, IIT-Bombay (mukherji@iitb.ac.in)

Ref. Quantitative Human Physiology by Joseph Feher

When the strength of depolarization reaches beyond a threshold it does not

matter any more .. It generates an action potential.. The shape of which is
approximately the same. However latency might change.

Effect of stimulus strength (above threshold) on Latency

Near the origin there can be

certain differences that have
to do with how fast Em
reaches the threshold (since
Em is not an exact duplicate of
the stimulating potential
capacitance effects)

S. Mukherji, IIT-Bombay (mukherji@iitb.ac.in)

Ref. Quantitative Human Physiology by Joseph Feher

Once an action potential is

generated, it can be seen at
points away from the point of
origin.. This is called
propagation. At points a bit
away the AP-s are
indistinguishable.

Changes in gNa and gK during the propagated action potential

as calculated by Hodgkin and Huxley

g Na

g Na
gK

g Cl

E Na

g Na

gK
gK

g Cl

EK

S. Mukherji, IIT-Bombay (mukherji@iitb.ac.in)

g Na

g Cl
gK

g Cl

ECl

Ref. Quantitative Human Physiology by Joseph Feher

Em

Hypothetical model of the voltage-gated tri-state Na+ channel

Saxitoxin also has similar

effects

S. Mukherji, IIT-Bombay (mukherji@iitb.ac.in)

Ref. Quantitative Human Physiology by Joseph Feher

Tetrodotoxin or TTX- binds

to Na+ channels and blocks
them.

Changes in the Na+ and K+ channels that give rise to the

action potential

Ref. Quantitative Human Physiology by Joseph Feher

S. Mukherji, IIT-Bombay (mukherji@iitb.ac.in)

The appearance of the action potential at later times down the

axon from the point of stimulation

Ref. Quantitative Human Physiology by Joseph Feher

S. Mukherji, IIT-Bombay (mukherji@iitb.ac.in)

Depolarization Can Spread passively

Ref. Quantitative Human Physiology by Joseph Feher

S. Mukherji, IIT-Bombay (mukherji@iitb.ac.in)

S. Mukherji, IIT-Bombay (mukherji@iitb.ac.in)

Electrotonic Spread of the Action Potential

The Hyperpolarizing or Depolarizing stimulii are not

faithfully reproduced in the axon the signal is distorted
due to the cable properties of the neuron.

S. Mukherji, IIT-Bombay (mukherji@iitb.ac.in)

The capacitances and the resistances due to the membrane are in parallel.

If we pass a constant current across the

membrane between any two nodes (lets
say A and B), a new membrane potential
is established (Em).
At some point x away from A or B, the
membrane potential Ex will depend on the
distance from the current source and the
time since the current was turned on.

Rm
where Rm is the resistance of a patch of membrane of unit area.
A

The axon cable can be considered to be a conductor and resistance

equation holds. However the external solution has very large
(undetermined) cross sectional area .. So effectively Ro is zero.
S. Mukherji, IIT-Bombay (mukherji@iitb.ac.in)

Currents at a unit membrane area of membrane

i ( x) i ( x dx) im
im
So
i ( x) i ( x dx)

V ( x) Vr
dV
A Cm A
Rm
dt

Using A 2 a.dx where a is the radius

i ( x dx) i ( x)
V ( x) Vr
dV
2 a
Cm 2 a
dx
Rm
dt
as dx 0
di
V ( x) Vr
2 a
dx
Rm

S. Mukherji, IIT-Bombay (mukherji@iitb.ac.in)

Cm 2 a

dV
dt

Ref. Quantitative Human Physiology by Joseph Feher

V ( x) Vr
dV
A Cm A
Rm
dt

Here Vr is the
membrane
potential at rest at
which net
membrane current
is zero

Currents at a unit membrane area of membrane (2)

Using Ohm' s law through Ri
i

V ( x) V ( x dx)
Ri
a 2 dV
as dx
i dx

V ( x) V ( x dx)
dx a 2
0

Taking V ' V Vr
d 2V '
dV '
V'
dx 2
dx
is a space constant and
is time constant
2

Substituting in the earlier equation

2

a dV
2
i dx

V Vr
2 a
Rm

dV
2 aCm
dt

Rearranging
V Vr

Rm a 2 d 2V
2ai dx 2

Rm
dV
2 aCm
2 a
dt

Rm a
2 i

RmCm

At steady state, when dV/dt = 0,

the space constant defines the
way in which voltage varies with
distance

S. Mukherji, IIT-Bombay (mukherji@iitb.ac.in)

Currents at a unit membrane area of membrane (3)

At steady state, when dV/dt = 0, the space constant defines the way in which
voltage varies with distance.
dV/dt = 0 can happen when a constant current has been passed through the
membrane for a time long enough to charge all the capacitors. In such a case
the earlier equation
2
2
d
V
'
dV
'
d
V'
2
V' 2
becomes
V
'
dx 2
dx
dx 2
the solution of which is V (V0 Vr )e x Vr

if we assume that V

V0 at x 0 and V

Vr at x

i.e. the voltage falls off exponentially from the point of application

S. Mukherji, IIT-Bombay (mukherji@iitb.ac.in)

Steady-state voltage as a function of distance from the point

of injection in myelinated and unmyelinated nerve fibers

Rm a
2 i

RmCm

Ref. Quantitative Human Physiology by Joseph Feher

S. Mukherji, IIT-Bombay (mukherji@iitb.ac.in)

Saltatory Conduction

Ref. Quantitative Human Physiology by Joseph Feher

What happens if the myelin sheath degrades or is lost ?

S. Mukherji, IIT-Bombay (mukherji@iitb.ac.in)

Electrically-coupled calcium signaling

S. Mukherji, IIT-Bombay (mukherji@iitb.ac.in)

Ligand-gated ion channels

S. Mukherji, IIT-Bombay (mukherji@iitb.ac.in)

Motor Neurons

Activates skeletal muscles

Receives thousands of inputs from other cells
o

Postsynaptic potentials can be Excitatory (EPSP) or Inhibitory (IPSP)

o
o

Upon excitation the presynaptic cell releases a neurotransmitter that

binds to the post synaptic cell and modulates ligand gated ion channels.
Neurotransmitters can be ionotropic i.e. directly alter ion conductances
or metabotropic that affect other targets which in turn affect ion
conductances.
Excitatory may work through increasing the Ca channel conductance
Inhibitory might work by increasing K or Cl channel conductance.

AP-s in motor neurons originate in the Axon Hillock

Motor Neurons integrate multiple inputs to initiate AP-s

S. Mukherji, IIT-Bombay (mukherji@iitb.ac.in)

Spatial and Temporal summation in a Motor Neuron

S. Mukherji, IIT-Bombay (mukherji@iitb.ac.in)

Conduction of Impulses from Nerves to Muscles

Motor Neuron 1 innervates
Muscles fibers A, B and C.
Motor Neuron 2 innervates D
and E.
The motor neurons can fire
independently or together. In
the latter case, larger force is
generated.

S. Mukherji, IIT-Bombay (mukherji@iitb.ac.in)

Fig. 3.5.2. Electron Micrograph of Muscle

A Anisotropic
I- Isotropic
H Helles (clear)
Z Zwischen (between)
M - Middle

S. Mukherji, IIT-Bombay (mukherji@iitb.ac.in)

Microscopic Appearance of Muscle

A - Anisotropic
I - Isotropic
H - Helles (clear)
Z - Zwischen (between)
M - Middle

S. Mukherji, IIT-Bombay (mukherji@iitb.ac.in)

Structure of the Sarcoplasmic Reticulum around the myofibril

S. Mukherji, IIT-Bombay (mukherji@iitb.ac.in)

Structure of the neuromuscular junction

S. Mukherji, IIT-Bombay (mukherji@iitb.ac.in)

Release of acetylcholine at the neuromuscular

junction

S. Mukherji, IIT-Bombay (mukherji@iitb.ac.in)

Duration of action potential, Ca transient and force in a twitch

S. Mukherji, IIT-Bombay (mukherji@iitb.ac.in)

S. Mukherji, IIT-Bombay (mukherji@iitb.ac.in)