Resting Membrane Potential & Action

Potential

Presented
By
Jere Methuselah
 Objectives
 By the end of this lectures the student should be able to:
1. Define the following terms:
I. Membrane Potential
II. Resting Membrane Potential
III. Action Potential
2. Explain why some membranes are excitable.
3. Describe the electrochemical basis of RMP.
4. Describe the mechanism of generation and propagation of AP.
5. Describe conduction along nerve fibers, role of myelination and
how nerve fibers are classified.
 Excitable Tissues
• Tissues which are capable of generation and
transmission of electrochemical impulses along the
membrane
Nerve Muscles
 Excitable
tissues
excitable Non-excitable

neuron
Red cell
GIT
muscle

•RBC
•Nerve
•Intestinal cells
•Muscle
•Fibroblasts
•Skeletal •Adipocytes
•Cardiac
•Smooth
 Membrane potential

• A potential difference exists across all cell membranes

• This is called
– Resting Membrane Potential (RMP)
 Membrane potential

– Inside is negative with respect to the outside

– This is measured using microelectrodes and oscilloscope
(VOLTMETER)
– This is about -70 to -90 mV
 Excitable tissues

excitable Non-excitable

neuron
Red cell
GIT
muscle
• Non-excitable tissues have less
• Excitable tissues have more negative RMP
negative RMP (- 70 mV to - 90 -53 mV epithelial cells
-8.4 mV RBC
mV)
-20 to -30 mV fibroblasts
-58 mV adipocytes
Resting Membrane Potential

• This depends on the following factors:

1. Ionic distribution across the membrane
2. Membrane permeability
3. Other factors
• Na+/K+ pump
 Ionic distribution
Na+ Cl-

K+ Pr -

• Major ions
– Extracellular ions
• Na+, Cl-
– Intracellular ions
• K+, Proteins
 Membrane permeability
Na+
Out

In
K+

• Leaky channels (K+/Na+ leak channels)

– More permeable to K+
– Allows free flow of ions
• In the resting state K+ permeability is 100 times more than that of Na+
 Na+/K+ pump
2 K+

ATP 3 Na+ ADP

• Active transport system for Na+-K+ exchange using energy

• It is an electrogenic pump since 3 Na+ efflux coupled with 2
K+ influx
• Net effect of causing negative charge inside the membrane
 Factors contributing to RMP

• One of the main factors is K+ efflux (Nernst Potential: -94mV)

• Contribution of Na+ influx is little (Nernst Potential:+61mV)

• Na+/K+ pump creates additional degree of negativity inside the

membrane (-4mV)

• Negatively charged protein ions remaining inside the membrane

contributes to the negativity

• Net result: -70 to -90 mV inside
Neuron Action Potentials
 Action potential
• An action potentials, are rapid changes in the
membrane potential that spread rapidly along the
plasma membrane of excitable cells to produce
physiological effects such as:

1. Transmission of impulse along nerve fibres

2. Release of neurotransmitters
3. Muscle contraction
4. Activation or inhibition of glandular secretion
 Characteristics of action potentials
1. Generation of action potential follows all-or-none principle
2. Refractory period lasts from time action potential begins
until normal resting potential returns
3. Continuous propagation
1. spread of action potential across entire membrane in series of
small steps
4. salutatory propagation
1. action potential spreads from node to node, skipping internodal
membrane
Each action potential begins with a sudden change from the normal resting
negative membrane potential to a positive potential and ends with an almost
equally rapid change back to the negative potential.

Stages of the action potential:

Resting Stage. It is the resting
membrane potential before the
action potential begins. The
membrane is “polarized”.

Depolarization Stage.

Repolarization Stage.
 Depolarization
Na+

Depolarization: The membrane suddenly becomes permeable to

Na+ ions, allowing tremendous numbers of positively charged
Na+ to diffuse to the interior of the axon (Upstroke)
 Repolarization
Na+

K+

Repolarization: Na+ channels begin to close and the K+ and Cl-

channels open. Rapid diffusion of K+ ions to the exterior and
influx of Cl- ions into the cell re-establishes the normal negative
resting membrane potential.
Reversal Potential
= + 35 mV

Local
Threhold Responses
Potential ( Firing Level )
= -50 to -65 mV

RMP= -90 mV

Q : What opens the voltage-

gated channels ? Opened by a
stimulus strong enough to
depolarize them to threshold Increasing Stimulation
• Threshold stimulus: The membrane potential at Acute subthreshold potential:
which occurrence of the action potential is Stimulus that results only in local
inevitable. depolarisation (acute local potentials)
when stimulus is below the threshold.

Local
Responses

All-or-nothing principle:
Once threshold value for excitation is reached a full AP is produced, its intensity can not be increased
by increasing stimulus intensity.
 Types of transport channels through the nerve membrane:

⮚ Voltage gated Na+ channels

⮚ Voltage gated K+ channels

 The Na+ Voltage-Gated Channel

• This channel has 2 gates:

• one on the outer side of the
membrane and is called the
activation gate.
• Another one on the inner side of
membrane called the inactivation
gate .
• This channel has 3 states :
● (1) Resting state : in the resting cell,
when the MP = RMP = -70 to - 90 mV
● the activation gate is closed
● this prevents entry of Na+ to the
interior of the cell through this gate.
 Activated State of Sodium Channel
 (2) Activated state :
• when a Threshold Depolarizing
Stimulus moves the MP from its resting
value (-90 mV ) to its Threshold value
(-65 to -55mV)
• this opens the activation gate , and
now the Na+ channel is said to be in
the Activated State
• (NB in this case BOTH the activation
gate & inactivation gate are open)
• permeability to Na+ becomes
increased 500 to 5000 times Na+ influx
• Na+ flows into the cell in large
amounts.
 Inactivated State of Sodium Channel
● (3) Inactivated state:
● A few milliseconds after the
activation gate opens, the
channel becomes inactivated:
● At the peak of AP the
inactivation gate will close the
inactivation gate will not open
by a second stimulus & the cell
becomes Refractory) to
another stimulation.
● in this case, while the
● This goes on until the MP has activation gate is still open,
gone back to its resting (RMP) the inactivation gate is
level (-70 to - 90mV). closed .
 Voltage gated Na+ channels

• At rest: the activation gate is

closed and the inactivation
gate is open.

• During the upstroke of the

action potential: both gates
local anesthetic lidocaine blocks this channel
are open and Na+ flows into
the cell down its
electrochemical potential
gradient.

• During repolarization: the

activation gate remains open
but the inactivation gate is Cannot elicit new AP

closed.
 Voltage gated K+ channels

 This channel has one gate only.

 During the resting state, the gate
of the potassium channel is closed
and potassium ions are prevented
from passing through this channel
to the exterior.

 Shortly after depolarization, when

the sodium channel begins to be
inactivated, the potassium
channel opens leading to K+ exits
(Efflux) Repolarization
Hyperpolarization: Why?
For a brief period following
repolarization, the K+
conductance is higher than at
rest. Na/K Pump brings
membrane potential
back to its resting value
Na+ - K+ ATPase pump now starts
to move Na+ out & K+ in against
their concentration gradient.
Hyperpolarization
 Refractory Periods
Two stages
• Absolute refractory period
• The period during which a
second action potential Higher K+
cannot be elicited, even Closure of
conductance than
with a strong stimulus. the
inactivation is present at rest
gates of
• Relative refractory period the Na+
• Can trigger new action channel
potential if stimulus is very
strong.
Propagation of the action potential
 Conduction Velocity
It is the speed at which action potentials are conducted
(propagated) along a nerve or muscle fiber.

Mechanisms that increase conduction velocity along a nerve:

1- Nerve diameter.
The larger the diameter, the faster the transmission,
Because:
-Large fiber offers Less resistance to local current flow
& more ions will flow.

Faster conduction Slower conduction

 Conduction Velocity
Mechanisms that increase conduction velocity along a nerve:
2- Myelination.
Myelin is an insulator that makes it more difficult for charges to flow
between intracellular and extracellular fluids.

- The layers of Schwann cell

membrane contain the lipid
substance sphingomyelin
which is excellent electrical
insulator that decreases ion
flow through the membrane.
- Node of Ranvier: small
uninsulated area where ions
can flow with ease.
Saltatory Conduction
It is the jumping of action potentials from one node of
ranvier to the next as they propagate along a
myelinated fiber.
Value:-
1- Increases conduction velocity.
2- Conserves energy for axon because only nodes depolarize.
 What happens if myelination is lost?
• Multiple sclerosis
– Autoimmune disease
(Immune system attacks the
myelin sheaths surrounding
axons as well as the axons
themselves).
– Usually young adults
– Blindness, problems
controlling muscles
• Ultimately paralysis
• Scar tissues (scleroses) replaces
some damaged cells.
Assignment
 Discuss the following:
1. NERNST EQUATION
2. GOLDMAN – HODGKIN KATZ EQUATION
 The End