2. Action potentials are signals which triggers
communication with surrounding cells!
WHAT IS ACTION POTENTIAL?
Excitable cells!
Neurons communicate by a combination of electrical and chemical signaling.
Generally, information is integrated and transmitted along the processes of a
single neuron electrically and then transmitted to a target cell chemically. The
chemical signal then initiates an electrical change in the target cell.
3. EXCITABLE CELLS ?
NEURON ENDOCRINE
CELLS
MUSCLE CELLS
EXCITABILITY; The ability of generating and conducting action
potential.
CONDUCTION CONTRACTION
SECRETION
4. The unequal distribution of ions
Na+
is more concentrated outside the cell
K+
is more concentrated inside the cell
+
+
+ +
+
+
+
-
-
-
- -
-
- +
Na+
K+
Electro-Chemical Equilibrium
5. Ions and the Resting Potential
• Ions are electrically-charged molecules e.g. sodium (Na+
), potassium (K+
),
chloride (Cl-
).
• The resting potential exists because ions are concentrated on different sides
of the membrane.
• Na+
and Cl-
outside the cell.
• K+
and organic anions inside the cell.
inside
outside
Na+
Cl-
Na+
K+
Cl-
K+
Organic anions
(-)
Na+
Na+
Organic anions
(-) Organic anions
(-)
6. Ions and the Resting
Potential/Diffusion
Potential
7. Na
Na
K
K
Ca
Ca
INTRACELLULAR-EXTRACELLULAR
ION CONCENTRATIONS
intracellular
extracellular
3 Na
2 K
ATP
Extracellular
concentration
(mM)
Intracellular
concentration (mM)
THE RESTING MEMBRANE POTENTIAL
The resting membrane potential is the electrical potential difference across the plasma
membrane of a normal living cell in its unstimulated state.
How can we measure the resting membrane potential?
It can be measured directly by
the insertion of a microelectrode into the cell with a reference
electrode in the extracellular fluid.
8. EXCITABLE
CELL
-70 mV : Intracellular area is more negative than (70 mV) extracellular area!
(The majority of the ions in intracellular area are negative charged/the majority of
the ions in extracellular area are positive charged)
THE RESTING MEMBRANE POTENTIAL
9. Action potential size, shape, and timing may
vary widely between the different cell types, but
there are several common characteris- tics,
including the existence of a threshold for action
potential for- mation, all-or-nothing behavior,
overshoots, and afterpotentials.
Action Potential
11. The successive stages of the action potential
• Resting stage:
– the membrane is “polarized”
– -90 mV inside the membrane
• Depolarization stage: the potential
rapidly rising in the positive direction
– Great excess of Na ions = overshoot
• Repolarization stage:
– Na channels begin to close
– Rapid diffusion of K ions to the
exterior re-establishes the negative
resting potential
14. Nernst Potential
•Relation of the diffusion potential to
the concentration difference.
•The diffusion potential level across a
membrane that exactly opposes the
net diffusion of a particular ion
through the membrane is called the
Nernst Potential.
17. Na+
-K+
pump causes a large concentration gradient
• These gradients for each ion are
Na (outside): 142 mEq/L
Na (inside): 14 mEq/L
K (outside): 4 mEq/L
K (inside): 140 mEq/L
The ratios of the two respective ions:
Nainside
/Naoutside
: 0.1
Kinside
/Koutside
: 35
19. Origin of the Normal Resting Potential
•Contribution of the potassium diffusion potential
•Contribution of Na diffusion through the nerve membrane
•Contribution of the Na+
-K+
pump
•The net membrane potential with all these factors
operating at the same time is about -90 mV.
21. Briefly;
• Within a milisecond, the potential difference becomes great enough
to block further net K diffusion to the exterior, despite high K ion
concentration gradient.
• For K ions: in the normal mammalian nerve fiber, the potential
difference required is about -94 mV, with the negativity inside the
fiber membrane
• For Na ions: the potential should be about 61 mV positive inside the
fiber in order to block further net diffusion of Na ions to the inside.
22. Permeability to several different ions
When a membrane is permeable to several different ions,
the diffusion potential that develops depends on three
factors:
1) Polarity of the electrical charge of each ion
2) Permeability of the membrane
3) Concentrations of the respective ions on the inside and
outside of the membrane
Goldman equation
23. Membrane potential is not a
potential. It is a difference of two
potentials so it is a Voltage in fact.
Membrane Potential
“The term “membrane potential” refers
to the voltage difference that exists
across the plasma membrane. By
convention, the ECF is considered to be at
zero volts, or electrical “ground.”
24. Number of ions needed for membrane potential ?
• An incredibly small number of ions needs to be transferred
through the membrane to establish the normal “resting
potential” of a -90 mV inside the nerve fiber.
• i.e. only about 1/3,000,000 to 1/100,000,000 of the total
positive charges inside the fiber needs to be transferred.
• An equally small number of positive ions moving from outside
to inside the fiber can reverse the potential from -90 mV to as
much as +35 mV within 1/10,000 of a second.
25. Resting Membrane Potential of Nerves
• RMP of large nerve fibers is about -90 mV
• i.e. the potential inside the fiber is 90 mV more negative than the
extracellular fluid on outside of the fiber.
• Na+
-K+
Pump: This powerful system continually pumps Na ions to the
outside and K ions to the inside of the cell.
• The membrane is about 100 times more permeable to K ions than Na.
26. Nerve Action Potential
• Nerve signals are transmitted by action potentials.
• They are rapid changes in the membrane potential
that spread rapidly along the nerve fiber membrane
27. Action Potential >>>>>>>>>>>> Ion Conductivity
Voltage gated channels are responsible for generating and conducting action
potential.
28. A, The nongated channel remains open,
permitting the free movement of ions across
the membrane.
B, The ligand-gated channel remains closed (or
open) until the binding of a neurotransmitter.
C, The voltage-gated channel remains closed
until there is a change in membrane potential.
The three types of ion channels
29. GENERAL STRUCTURE
OF
VOLTAGE GATED SODIUM CHANNELS
1.Pore for ion transition
2. Sensor which senses voltage changes
3. Gate, regulates ion transition
4. Selective filter, decides which ion
will pass or not.
1
2
3
4
30. TYPES OF VOLTAGE GATED ION CHANNELS
VOLTAGE GATED SODIUM (Na) CHANNEL
VOLTAGE GATED POTASSIUM (K) CHANNEL
VOLTAGE GATED CALSIUM (Ca) CHANNEL
31. Voltage Gated Na and K Channels
• The necessary actor in causing both depolarization
and repolarization of the nerve membrane during AP
is the voltage-gated Na channel
• Voltage-gated K channel is also important
• These two voltage-gated channels are in addition to
the Na+
-K+
pump and K+
-Na leak channels
33. Voltage Gated Na Channel: Activation and Inactivation
• A rise in memmbrane potential (MP) in positive
direction
• A voltage between -70 and -50 mV causes a
sudden conformational change in the activation
gate
• The same increase in voltage that opens the
activation gate also closes the inactivation gate.
• So, Na ions no longer can pour to the inside of
membrane
• Inactivation gate will not re-open until the MP
returns to or near the original resting MP level.
34. Voltage Gated K Channel and Its Activation
• During the resting state, K gate is closed
• When MP rises from -90 mV toward zero, this
voltage change causes a conformational
openning of the gate and allows increased K
diffusion outward through the channel.
• K channel opens just at the same time that Na
channel is beginning to close because of
inactivation
35. Summary of the Events That Cause Action Potential
• Influx of Na ions (5000 fold
increase in Na
conductance
• Na channels begin to close
and K channels to open
• Rapid loss of K ions to the
exterior
• Returning to the baseline
level
36. The states of voltage-gated sodium and potassium
channels correlated with the course of the action
potential.
A, At the resting membrane potential, both channels are
in a closed, resting state.
B, During the depolarizing phase of the action potential
the voltage-gated sodium channels are activated (open),
but the potassium channels open more slowly and,
therefore, have not yet responded to the depolarization.
C, During the repolarizing phase, sodium channels
become inactivated, while the potassium channels become
activated (open).
D, During the after hyperpolarization, the sodium
channels are both closed and inactivated, and the
potassium channels remain in their active state.
Eventually, the potassium channels close and the sodium
channel inactivation is removed, so that both channels are
in their resting state and the membrane potential returns
to resting membrane potential. Note that the
voltage-gated potassium channel does not have an
inactivated state
37. Initiation of the Action Potential
• A positive feedback vicious
cycle opens the Na channels
• Threshold for initiation of the
action potential
• A sudden rise in membrane
potential of 15 to 30 mV is
required
• -65 mV is the threshold for
stimulation
38. Propagation of the Action Potential
• Action potential occurs at one spot on the
membrane
• It then excites adjacent portions of the
membrane, resulting in propagation of the AP
along the membrane.
• Direction of propagation: in all directions from the
stimulus, until the entire membrane is
depolarized.
• All-or-Nothing Principle: Sometimes AP reaches
a point where it does not generate sufficient
voltage to stimulate the next area of the
membrane.
• When this happens, the spread of polarization
stops.
1
39. Plateau in Some Action Potentials
• In some cases, the excited membrane does not
immediately repolarize after depolarization.
• Instead, the potential remains on a plateau near the peak
of the spike potential for some miliseconds, then
depolarization begins.
• This happens in the cardiac muscle fibers (0.2 to 0.3 sec
delay)
• Two types of channels in the heart muscle:
• Voltage-gated Na channels
• Voltage-activated Ca-Na channels
• Second factor: voltage-gated K channels are slower than
usual to open
40. Special characteristics of signal transmission in nerve trunks
• Myelinated and unmyelinated nerve fibers
• Schwann cell and sphingomyelin
• Node of Ranvier
41. “Saltatory” conduction in myelinated fibers from node to
node
• No ions can flow through the thick myelin sheats
• They can flow easily through the nodes of Ranvier
• Thus, action potential (AP) can only occur at the nodes
• The AP is conducted from node to node (which is called saltatory
conduction)
• Electrical current flows through the surrounding extracellular
fluid as well as through the axoplasm
• This mechanism
• Increases the velocity
• Conserves energy
Node of Ranvier and Action Potential
Node of Ranvier
Myelin sheath
42. “Saltatory” conduction in myelinated fibers from node to
node
* Velocity of conduction in nerve fibers varies from 0.25 m/sn (unmyelinated) to
100 m/sn (myelinated)
43. Excitation (process of eliciting action potential)
What causes the action potential?
Any factor that causes Na ions to begin to diffuse inward the
membrane in sufficient numbers can set off automatic regenerative
openning of Na channels.
1) Mechanical disturbance of the membrane (nerve endings in the skin)
2) Chemical effects on the membrane
3) Electrical current to transmit signals between muscle cells in the
heart and intestine.
44. Refractory Period
• A new potential cannot occur in
an excitable fiber as long as the
membrane is still depolarized
from the previous AP.
• The period during which a
second AP cannot be elicited
(even with a strong stimulus) is
called absolute refractory period.
46. Excitation of a Nerve Fiber by Negatively Charged Metal Electrode
• Application of electricity to the nerve or muscle surface through
two small electrodes (one negative and one positively charged)
• The excitable membrane becomes stimulated at the negative
electrode
• The negative current from the electrode decreases the voltage
on the outside of membrane to a negative value nearer the
negative potential inside the fiber.
