Membrane Potentials and Action
Potentials
“Diffusion Potential“ caused by Ion concentration difference on the two sides of the membrane
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Example: K+ concentration is great inside a nerve cell membrane than on the outside
Membrane is only permeable to K+ ions
K+ ions diffuse across the membrane along the concentration gradient therefore creating
negative inside and a positive outside
Within a ms the potential difference between the inside and the outside, called the
diffusion potential, becomes great enough to block further net K+ diffusion to the
exterior, despite the high K+ ion concentration gradient.
In normal mammalian nerve fibers, the potential difference required to stop the diffusion
is about 94 millivolts with negativity inside the fiber membrane (for K+ ions)
Concentration difference of ions across a selectively permeable membrane can, under appropriate
conditions, create a membrane Potential.
Relation of the Diffusion Potential to the concentration difference – Nernst Potential
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Diffusion potential level across a membrane that exactly opposes the net diffusion of a
particular ion through the membrane is called the Nernst potential for that ion.
1) Magnitude of this Nernst potential is determined y the ratio of the
concentrations of that specific ion on the two sides of the membrane
2) The greater this ratio is, the greater the tendency for the ions to diffuse in one
direction and therefore the greater the Nernst potential required to prevent
addition net diffusion
𝐶𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛 𝑖𝑛𝑠𝑖𝑑𝑒
3) 𝐸𝑀𝐹(𝑚𝑉) = ±61 log 𝐶𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛 𝑜𝑢𝑡𝑠𝑖𝑑𝑒
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This is the Nernst equation.
Used to calculate Nernst potential for any univalent ion at 98.6°F (37°C)
EMF= Electromotive Force
Sign of the potential is positive if the ion diffusing from the inside to the
outside is a negative ion, if the ion is positive the Nernst potential is
positive.
For this formula, it is assumed that the potential in the extracellular fluid
outside the membrane remains at zero potential and the Nernst
equation potential is the potential inside the membrane
Resting membrane potential of nerves
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The resting membrane potential of a nerve fiber when not transmitting nerve signals is
about -90mV. This means that the inside of the cell is 90mV more negative compared to
the outside.
Active Na+ and K+ transport:
1) Na+-K+-Pump (electrogenic pump)
2) Causes large concentration gradients for Na+ and K+ across the resting nerve
membrane.
Substance Outside Cell Inside Cell
Na+
142 mmol/l 14 mmol/l
K+
4 mmol/l
140 mmol/l
+
+
3) Ratio Na inside/ Na outside=0.1
4) Ratio K+inside/ K+outside=35
5) Na+ and K+ are able to leak through channel proteins, called potassium-sodium
“leak” channel
Nerve Action Potential
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APs are rapid changes in the membrane potential
APs begin with a sudden change from a normal resting negative membrane potential to a
positive potential and end with a rapid change back to the negative potential
1 Resting Stage:
a. Is the resting membrane potential before the AP begins
b. Membrane is polarized
2 Depolarization Stage:
a. Membrane becomes permeable to Na+ ions
b. Inflowing positive Na+ ions depolarize the membrane
c. In large nerve fibers, the great excess of positive Na+ ions moving to the
inside cause the membrane potential to actually “overshoot” beyond the
zero level.
3 Repolarization Stage:
a. Shortly after the membrane became permeable to Na+ ions, the sodium
channels begin to close and the K+ open more than normal
b. K+ rapidly diffuses to the exterior  causes a re-establishment of the
normal negative resting membrane potential  repolarization
Voltage – gated sodium and potassium channels
1)
Voltage – gated sodium channel – activation and inactivation
a. Two gates:
i. One near the outside: Activation gate
ii. One near the inside: Inactivation gate
b. In the state of a normal resting membrane (-90mV) the activation gate is closed
and the inactivation gate is open.
c. Example: activation of Na+ channels:
i. When the membrane potential becomes less negative, it reaches a
voltage (usually between -70 & -50 mV) that cause a sudden
conformational change in the activation gate
ii. The conformational change causes the activation gate to flip all the way
to the open position  activation state; sodium ions pour to the interior
d. Example: inactivation of Na+ channels:
i. Same increase in voltage that caused the activation gate to open also
causes the inactivation gat to close (a few 10000ths of a second after the
activation gate opens)
ii. Na+ ions no longer pour into the interior
iii. The inactivation gate will not reopen until the membrane potential
returns to or near the original resting membrane potential level
2) Voltage – gated potassium channel – activation and inactivation
a. During the resting state, the gate of the K+ - channel is closed
b. When the membrane potential rises towards zero, this voltage change causes a
conformational change, which in turn opens the K+ - channel gate
c. K+ ions diffuse out of the cell
d. Because of the slight delay in the opening of the K+ channels, for most part, they
just open at the same time as the Na+ - channels begin to close
e. The decrease in Na+ entry into the cell and the simultaneous increase in K+ exit
from the cell combine to speed up the repolarization process
Role of other ions during the AP
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Anions (negative ions) and Ca2+
1) Impermeant negatively charged ions (anions) inside the nerve axon:
a. Inside the axon are many anions that cannot go through the
membrane channels. Inclusive the anions of protein molecules,
organic phosphate compounds, sulfate compounds
b. Because these ions cannot leave the interior of the axon, any deficit
of positive ions inside the cell leaves an excess of these impermeant
anions  responsible for the negative charge inside
2) Calcium Ions
a. Almost all body cell membrane do have Ca2+ - pumps
b. Ca2+ serves, along with Na+, in some cells to cause most of the AP
c. The Ca2+ pump pumps Ca2+ from the interior to the exterior or into
the endoplasmic reticulum
d. There are also voltage – gated Ca2+ channels
i. Slightly permeable to Na+ ions
ii. When they open Ca2+ and Na+ ions flow to the interior of the
fiber (Ca2+ – Na+ Channel)
iii. Ca2+ channels are slow channels  because they become
slowly activated
iv. Ca2+ - channels are very numerous in smooth and cardiac
muscle cells
v. Increased permeability of Na+ - channels when there is a
deficit of Ca2+ ions
1. Concentration of Ca2+ ions in the extracellular fluid
also has a profound effect on the voltage level at
which sodium channels become activated
2. Decrease in Ca2+ level causes Na+ channels to
become activated by very little increase of the
membrane potential  nerve fiber becomes highly
excitable; sometimes discharging repetitively
without provocation
3. Ca2+ concentration only need to fall 50% below
normal value before spontaneous discharge occurs
in some peripheral nerves, often causing muscly
tetany
Initiation of the AP
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If any event causes enough initial rise in the membrane potential, from -90 mV towards
zero, the rising voltage itself causes voltage – gated Na+ - channels to open  Na+ ions
flow to the interior  causes a further rise in membrane potential  opening of more
Na+ - channels  even more Na+ ions enter the cell. This process is called positive
feedback / vicious cycle
Shortly after causing the Na+ - channels to open, the rise in membrane potential causes
Na+ - channels to close and K+ - channels to open  the AP terminates
Threshold for initiation of AP
1) AP will not occur until an initial rise in membrane potential is great enough to
create the vicious cycle
 Occurs when the number of Na+ ions entering the cell becomes greater
than the number of K+ ions leaving the cell
2) A rise in membrane potential of 15 – 30 mV is usually required
Propagation of the AP
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AP elicited at any point on an excitable membrane usually excites adjacent portions of
the membrane
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“local circuit” of current flow from the depolarized areas of the membrane to the
adjacent resting membrane areas
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The mechanism of “local circuit” is that positive charges are carried by inward diffusing
Na+ ions through the depolarized membrane and then for several mm in both directions
along the axon (see drawing)
In this way, the depolarization process travels along the entire length of the nerve
(impulse)
A membrane has no single direction of propagation
Depolarization process travels over the entire membrane if conditions are right, or not at
all if conditions are not right  all or nothing principle
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Safety factor for propagation  the ratio of AP to threshold for excitation must be
greater than 1
Re-establishing Sodium and Potassium ion gradients after Aps are completed – Importance of energy
metabolism
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AP along a nerve fiber only reduces the concentration difference of Na+ and K+ inside and
outside of the cell very slightly
~100000 – 50 million impulses can be transmitted by large nerves before the
concentration difference reaches the point at which AP conduction ceases
Na+ – K+ pump re-establishes the Na+ – K+ membrane concentration differences
Pumps require energy in the form of ATP  metabolic process
Degree of activity of the Na+ – K+ pump is strongly stimulated if excess Na+ accumulates
inside the cell
Plateau in some APs
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Depolarized membrane does not repolarize immediately but potential remains on a
plateau near the peak
Occurs for example in heart muscle fibers
Prolongs the period of depolarization
The cause of a plateau is a combination of several factors
1) In the heart 2 types of channels enter the depolarization process:
 Voltage – gated Na+ – channels (fast channel; opening causes spike
portion [0 – 1])
 Voltage – gated Ca2+ – Na+ – channel (slow channel; opening causes
plateau portion [1 – 2])
2) Voltage –gated K+ – channels
 They open slower than usual
Rhythmicity of some excitable tissue – repetitive discharge
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Occurs in the heart, most smooth muscle cells and many neurons of the CNS
Rhythmical discharges are for example:
1) Rhythmical beat of the heart
2) Rhythmical peristalsis of the intestine
3) Neural events (rhythmical breathing)
Almost all excitable tissue can discharge repetitively if the threshold for stimulation of
the tissue cells is reduced low enough
Re-excitation process necessary for spontaneous rhythmicity
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For spontaneous rhythmicity to occur, the membrane even in its stable/natural state
must be permeable enough to Na+ ions (or to Ca2+ and Na+ ions via slow Ca2+ – Na+
channels) to allow automatic membrane depolarization
Myelinated and unmyelinated nerve fibers
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In general:
1) Large nerve fibers are myelinated
2) Small nerve fibers are not myelinated
3) Membrane of the axon conducts the AP
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Membrane of Schwann cells contain sphingomyelin which is an excellent isolator
Between the Schwann cells are Nodes of Ranvier
“Saltatory” Conduction in myelinated fibers from node to node
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Ions can flow between the nodes of Ranvier  therefore APs only occur between the
nodes of Ranvier
APs are conducted between the nodes of Ranvier and this is called saltatory conduction
Nerve impulses jump down the axon
Saltatory conductance increases the velocity of nerve transmission and conserves energy
because little ions flow during APs and therefore little metabolism is required to reestablish the Na+ – K+ concentrations
Mechanical, chemical and electrical effects can elicit an AP
Inhibition of excitability – “stabilizers” and local anesthetics
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Membrane stabilizing factors can decrease the excitability
1) Example: High extracellular fluid Ca2+ concentration decreases membrane
permeability to Na+ ions – calcium ions are said to be a “stabilizer”
2) Local anesthetics
 Procaine and tetracaine
 Most directly act on the activation gate of the Na+ – channels therefore
reducing the membrane permeability