Physiology Ch 5 p57-70
Membrane Potentials and Action Potentials
Diffusion Potential Caused by Ion Concentration Difference on 2 Sides of Membrane – K is
usually great inside a nerve fiber but low outside membrane
-if membrane permeable to K but not other ions, there is tendency for extra K to diffuse out,
positive charge  outside, creating electropositivity outside and electronegativity inside
because negative anions remain inside
-potential difference between inside and outside, diffusion potential, becomes great
enough to block further K diffusion out
-in normal nerve fiber, potential difference required is 94mV with negativity inside
-if membrane permeable to Na (high on outside, low on inside), net diffusion of Na will be inside
to create membrane potential of opposite polarity (negativity outside, positivity inside)
-potential rises enough to stop further influx of Na; potential is 61mV positive inside the fiber
Relation of Diffusion Potential to Concentration Difference – Nernst Potential – diffusion
potential across membrane that opposes net diffusion of particular ion through membrane is
called Nernst potential for that ion
-magnitude is determined by ratio of concentration of ion inside to outside; the greater the
ratio, the greater tendency for ion to diffuse in one direction, and the greater the Nernst
potential required to prevent additional net diffusion
EMF = +/- 61 * log (concentration inside/concentration outside)
-usually assumed that potential outside is 0, while potential inside is the Nernst potential, thus
when concentration of K ions inside is 10x that on the outside, Nernst potential is -61mV inside
Calculation of Diffusion Potential When Membrane is Permeable to Several Ions- if permeable
to several ions, diffusion depends on polarity of charge of each ion, permeability of membrane
to each ion (P), concentrations (C) on inside and outside; use the goldman equation:
-EMF = -61*log ((CNaPNa + CKPK + CClPCl) inside/ (CNaPNa + CKPK + CClPCl) outside)
-degree of importance of each ion is proportional to membrane permeability of each ion; if
membrane has 0 permeability to K and Cl, then the membrane potential becomes entirely
dominated by concentration gradient of sodium ions alone = Nernst potential for sodium
-positive ion concentration gradient from inside to outside causes electronegativity inside the
membrane
-chloride ion gradient from outside to inside causes negativity inside ell because excess negative
Cl diffusing in, leaving positive ions outside
Measuring the Membrane Potential – small pipette with electrolyte solution impaled through
cell membrane to interior, different electrode placed in extracellular fluid; voltage is measured
using a voltmeter
-electric potential outside membrane is 0, as electrode measures across membrane, it becomes
negative 90mV throughout fiber until the other membrane is reached, rising back to 0
-to create negative potential inside membrane, only enough positive ions to develop electric
dipole at membrane must be transported out; all remaining ions can be positive and negative,
and so only a SMALL NUMBER of positive ions need to be transported out to achieve -90mV
Resting Membrane Potential of Nerves – resting membrane potential of large nerve fibers
when not transmitting signals is about -90mV (potential inside fiber is 90mV more negative than
potential in the extracellular fluid on the outside of the fiber)
Active Transport of Na and K ions Through Membrane (Na/K Pump) – all membranes have an
Na/K pump that continually transports Na to outside and K ions inside; it is an electrogenic
pump because more positive charges are pumped to outside than inside (3 Na out for 2 K in),
leaving net deficit of positive ions on inside, causing net gradients of ions
Na outside: 142mN, inside: 14mN; K outside: 4mN, inside: 140mN
Ratios Na(in)/Na(out) = 0.1, K(in)/K(out) = 35
Leakage of K+ through Nerve Membrane – a channel protein called tandem pore domain,
potassium channel, or potassium leak channel in the nerve membrane causes K to leak out in a
resting cell
Origin of Normal Resting Membrane Potential:
1. Contribution of K+ Diffusion Potential – high ratio of potassium inside to outside (35:1),
Nernst potential for this ratio is -94mV inside the fiber
2. Contribution of Na+ Diffusion Potential – with the goldman equation and knowing that
membrane is more permeable to K than Na, Na contributes to equation to make net
potential inside membrane of -86mV
3. Contribution of Na-K Pump – continuous pump of 3 Na out and 2 K in causes loss of positive
charges from inside the membrane by an additional degree (-4mV total), causing total
membrane potential to be -90mV
Nerve Action Potential – nerve signals are transmitted by action potentials, rapid changes in
membrane potential that spread along nerve fiber membrane and caused by sudden change of
resting membrane potential to a positive potential and then reverts back to negative
1. Resting Stage – resting stage before potential begins, membrane polarized at -90mV
2. Depolarization Stage – membrane becomes permeable to Na, allowing Na to diffuse
inside and the -90mV is neutralized in the positive direction; excess sodium causes
membrane potential to overshoot and become positive 35mV
3. Repolarization – within 10000ths of a second after membrane becomes permeable to
Na, sodium channels close and K channels open, allowing K to diffuse out to re-establish
normal negative resting potential
Voltage-Gated Na and K Channels – involved in both depolarization and repolarization
Voltage-Gated Na Channel – channel has 2 gates – one near outside channel called the
activation gate, and another on inside called the inactivation gate. At -90mV, activation gate is
closed to prevent entry of Na ions to interior
Activation of Na Channel – when potential becomes less negative, moving from -90 to -70 or
negative 50, activation gate has conformational change flipping it to open state/letting Na influx
Inactivation of Na Channel – increase in voltage that opens the activation gate ALSO closes the
inactivation gate (10000th of a second later) to stop Na influx, and membrane potential recovers
-inactivation gate will NOT reopen until membrane potential returns to near resting state
Voltage Gated K channel and Activation – during resting state, gate of K channel is closed and K
ions are prevented from passing through this channel to the outside. Increase in membrane
potential above -90mV causes opening of gate allowing increased K diffusion out of channel;
open around the same time as Na channels to speed the repolarization process
Measuring Effect of Voltage on Opening/Closing Channels – Voltage Clamp – a voltage clamp
measures flow of ions through different channels
-this method allows one electrode to measure voltage of membrane potential, and one
electrode conducts current in or out of the fiber
-current injected must equal but oppose polarity of net current flow through channels
-investigator adjusts ion concentration on either side of membrane and repeats the study
-another means of studying flow of ions is to block one type of channel
-tetrodotoxin blocks Na channels
-tetraethylammonium blocks K channels
Summary of Events that Cause an Action Potential – during resting state, conductance of K ions
is 100x as great as conductance of Na ions caused by leakage through leak channels; at onset of
action potential, there is 5000-fold increase in Na conductance, and the inactivation process
closes Na channels in another fraction of millisecond, also causes voltage gated K channels to
open to return membrane potential to normal (negative) state
Roles of Other Ions During Action Potential – inside the axon there are many negatively
charged ions that cannot go through channels, called impermeant anions such as phosphates,
sulfates; so a deficit in positive ions causes net negative charge inside of fiber
Calcium Ions – membranes of all cells have a Ca pump similar to Na pump, meant to pump Ca
ions from interior to exterior and creating a Ca gradient of 10,000-fold
-there are voltage-gated Ca channels causing tremendous diffusion gradient for passive flow of
Ca into cells; when stimulated by potential, channels open allowing calcium to flow inside
-major function of voltage-gated calcium channel is to contribute to depolarizing phase in some
cells
-gating of Ca channels is SLOW, requiring 10-20x longer for activation to provide a
longer, more sustained depolarization
-Na channels are fast (initiate fast action potential)
-Ca channels are numerous in cardiac and smooth muscle (Na channels not present)
Increased permeability of Na channels when there is deficit of Ca ions – when there is a deficit
of Ca ions, Na channels become activated by small increase of membrane potential and nerve
fiber becomes highly excitable and can discharge repetitively (can cause tetany)
Initiation of Action Potential – A positive feedback cycle opens Na channels; if membrane goes
undisturbed, no action potential occurs, but any event causing enough rise in membrane
potential from -90mV can open voltage gated Na channels and allow rapid influx of Na to further
depolarize membrane (positive feedback), and continues until all channels have been opened
Threshold for Initiation of Action Potential – action potential will not occur until initial rise is
great enough to cause the positive feedback described before; sudden rise of 15 to 30mV in
membrane potential is required (up to -65mV) usually causes action potential (-65mV is called
threshold for stimulation)
Propagation of Action Potential – an action potential at one spot can excite adjacent portions of
membrane, resulting in propagation along the membrane
-positive electrical charges are carried by inward-diffusing Na ions through depolarized
membrane and then for several mm in both directions along core of axon, causing new Na
channels to open in those areas, and then causes more depolarization; nerve impulse
Direction of Propagation – action potential travels in all directions away from stimulus until
entire membrane has been depolarized
All-or-Nothing Principle – one an action potential has been elicited, the depolarization process
travels over entire membrane if conditions are right, or it does not travel at all if the conditions
are not right
-occasionally an action potential reaches a point on membrane that cannot be excited to
threshold, and so the spread of depolarization stops
-continued propagation of an impulse can only occur if ratio of action potential to threshold for
excitation is greater than 1, called the safety factor
Re-establishing Na and K Gradients After Action Potentials are Completed – 100,000-50 million
impulses can be transmitted by large nerve fibers before the concentration reach a point that
action potential conduction ceases
-re-establishing Na and K membrane concentration is achieved with Na-K pump; pumping 3 Na
out and 2 K in and using ATP for energy to drive the process
-Na/K ATPase is strongly stimulated when excess Na ions accumulate inside cell membrane
-pumping activity increases in proportion to the 3rd power of intracellular sodium
Plateau in Some Action Potentials – sometimes the membrane does not repolarize right after
depolarization, but plateaus for a few ms and later repolarizes; occurs in heart muscle fibers
where plateau lasts for 0.2-0.3s and causes contraction of heart muscle to last for this same
period
-caused by fast acting sodium channels and slow acting calcium-sodium channels
-opening of fast channels causes spoke portion, whereas opening of Ca channels causes plateau
by Ca entering the membrane
-second factor is that voltage gated K channels slower to open too
Rhythmicity of Some Excitable Tissues – Repetitive Discharge – repetitive discharges occur in
heart, most smooth muscle, and many neurons of CNS, which cause rhythmical beating of heart,
peristalsis of intestines, and rhythmical control of breathing
Re-Excitation Process Necessary for Spontaneous Rhythmicity – membrane must be permeable
enough to Na ions (or to Ca and Na together) to allow automatic membrane depolarization
-heart resting membrane potential is -60mV, not enough negativity to keep Na/Ca channels
closed
-Na flows in, opening channels for more Na to come in and permeability increases more until
action potential is formed, and then the membrane repolarizes
-spontaneous excitability occurs again after a few ms to cause new action potential
-after action potential, membrane becomes more permeable to K+ to increase outflow, causing
a state of hyperpolarization, during which self-reexcitation will not occur
-increased K conductance slowly disappears, and membrane depolarizes again
Myelinated and Unmyelinated Fibers – large fibers are myelinated, small fibers are
unmyelinated; average nerve trunk contains twice as many unmyelinated fibers as myelinated
fibers
-central core of myelinated fiber is axon, filled with axoplasm, a viscid intracellular fluid; myelin
sheath is thickeer and every 1-3mm down length is a node of ranvier
-myelin sheath is deposited around peripheral axons by Schwann cells in the following manner:
Schwann cell envelops axon, rotates around axon many times  lays down multiple layers of
membrane containing sphingomyelin, which is an excellent insulator to decrease ion flow
through membrane
-ions can still flow around nodes of ranvier
Saltatory Conduction in Myelinated Fibers from Node to Node – ions can flow with ease
through nodes of Ranvier; therefore action potentials can ONLY occur at the nodes, where it
jumps from node to node – called saltatory conduction
-current flows inside axoplasm as well as from node to node on the extracellular space; nerve
impulse jumps around
-by causing depolarization to jump long intervals, this increases velocity of conduction by 5-50fold
-saltatory conduction conserves energy for axon because only nodes depolarize and doesn’t
activate as many Na/K pumps to restore membrane potential
-allows repolarization to occur without many ions needing transfer
Velocity of Conduction in Nerve Fibers – varies from 0.25m/s in unmyelinated fibers to 100m/s
in large myelinated fibers
Excitation – Process of Eliciting Action Potential – any factor causing Na diffusion inward can
open channels, including mechanical disturbance of membrane, chemical effects of membrane,
passage of electricity through membrane
-mechanical pressure excites nerve endings in skin, chemical neurotransmitters to nerve cells
-can excite nerve fiber by using a negatively charged electrode sending signal to positive
electrode, which causes net potential that opens Na channels and causes action potential
Threshold for Excitation and Acute Local Potentials – weak, negative stimulus may not be able
to excite a fiber; when voltage is increased, excitation does take place
-small, local potentials that don’t reach threshold are called acute local potentials and if they
fail to make action potential, they are called acute subthreshold potentials
Refractory Period after Action Potential – a new action potential cannot occur in an excitable
fiber as long as membrane is still depolarized from previous action potential because sodium
channels become inactivated and NO amount of excitation will open the inactivation gates
-period when second action potential cannot be elicited is called absolute refractory period
Inhibition of Excitability – Stabilizers and Local Anesthetics – membrane-stabilizing factors can
DECREASE excitability; a high extracellular Ca concentration decreases membrane permeability
to Na ions and reduces excitability – Ca ions are said to be stabilizers
-Local Anesthetics – most important stabilizers are local anesthetics, such as procaine and
tetracaine which act on activation gates to make them more difficult to open and reduce
membrane excitability; safety factor is <1
Recording Membrane Potentials and Action Potentials
Cathode Ray Oscilloscope – membrane potential changes rapidly during course of action
potential, and so a cathode ray oscilloscope helps capture rapid fluctuations in potential
-cathode ray tube is an electron gun and fluorescent screen against which electrons are fired
-two electrically charged plates on both sides of electron beam (above and below and side to
side)
-electrical current can be bent up or down in response to electric signals coming from
recording electrodes from nerves
-stimulus artifact is seen because it is the electricity needed to elicit action potential in
the nerve fiber