BASIC PHYSICS OF MEMBRANE POTENTIALS:
MEMBRANE POTENTIALS CAUSED BY ION CONCENTRATION
Differences Across a Selectively
- K inside membrane more outside less
- K moves outside then negative potential creates inside because of other anions that are present inside the membrane
- The potential difference between the inside and outside called the diffusion potential
- In the normal mammalian nerve fiber, the potential difference is about 94 millivolts, with negativity inside the fiber membrane
- In the case of sodium more sodium outside and less inside
- Na moves inside then creates positive potential inside.
- In the normal mammalian nerve fiber, the potential difference is about 61 millivolts, with positivity inside the fiber membrane.
RESTING MEMBRANE POTENTIAL
- The resting membrane potential of large nerve fibers when they are not transmitting nerve signals is about −90 millivolts.
- The potential inside the fiber is 90 millivolts more negative than the potential in the extracellular fluid on the outside of the fiber
Active Transport of Sodium and Potassium Ions Through the Membrane—The Sodium-Potassium (Na+K+) Pump.
- Electrogenic Na K pumps continuously transport Na ions outside in K ions inside
- More positive charges move outside than inside, Leaving a net deficit of positive ions on the inside and causing negative potential inside the cell membrane.
- The gradients of charges are below
Leakage of Potassium Through the Nerve Cell Membrane:
Channel proteins causes leakage of K ions even in resting membrane potential and also sometimes Na ions.
ORIGIN OF THE NORMAL RESTING MEMBRANE POTENTIAL:
Contribution of the Potassium Diffusion Potential
we assume that the only movement of
ions through the membrane are the diffusion of potassium
the Nernst potential is −94 millivolts
Contribution of Sodium Diffusion Through the Nerve
Minute diffusion of sodium ions through the K+Na+leak channels. The ratio of sodium ions from inside to outside the membrane is 0.1, which gives a calculated Nernst potential for the inside of the membrane of +61 millivolts.
the permeability of the membrane to potassium is about 100 times as great as its permeability to sodium. Using this value in the Goldman equation gives a potential inside the membrane of −86 millivolts, which is near the potassium
potential shown in the figure.
Contribution of the Na+K+ Pump.
Na+ K+pump provides an additional contribution to the resting potential.
continuous pumping of three sodium ions to the outside occurs for each two potassium ions pumped to the inside of the membrane. The pumping of more sodium ions to the outside than the potassium ions being pumped to the inside causes continual loss of positive charges from inside the membrane, creating an additional degree of negativity (about −4 millivolts additional) on the inside beyond that which can be accounted for by diffusion alone. Therefore, the net membrane potential when all these factors are operative at the same time is about −90 millivolts.
NEURON ACTION POTENTIAL
Nerve signals are transmitted by action potentials, which are rapid changes in the membrane potential that spread
rapidly along the nerve fiber 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.
The successive stages of the action potential are as follows.
The resting stage is the resting membrane potential before the action potential begins. The
membrane is said to be “polarized” during this stage. because of the −90 millivolts negative membrane potential that is present.
At this time, the membrane suddenly becomes permeable to sodium ions, allowing tremendous numbers of positively charged sodium ions to diffuse to the inside of the axon.
The normal “polarized” state of −90 millivolts is immediately neutralized by the inflowing positively charged sodium ions, with the potential rising rapidly in the positive direction a process called depolarization.
In large nerve fibers, the great excess of positive sodium ions moving to the inside causes
the membrane potential to actually “overshoot” beyond the zero levels and to become somewhat positive. In some
smaller fibers, as well as in many central nervous system neurons, the potential merely approaches the zero level
and does not overshoot to the positive state
Within a few 10,000ths of a second after the membrane becomes highly permeable to
sodium ions, the sodium channels begin to close, and the potassium channels open to a greater degree than normal. Then, rapid diffusion of potassium ions to the exterior re-establishes the normal negative resting membrane potential, which is called repolarization of the membrane.
VOLTAGE-GATED SODIUM AND
The necessary factor in causing both depolarization and repolarization of the nerve membrane during the action
potential is the voltage-gated sodium channel.
Activation and Inactivation of the
Voltage-Gated Sodium Channel
The Sodium channel has two gates one near the outside of the channel called the
activation gate and another near the inside called the inactivation gate. In -90 millivolts condition activation gate is closed which prevents any entry of sodium ions to the interior of the fiber through
these sodium channels.
Activation of the Sodium Channel
When membrane potential becomes less than -90 mv and reaches −70 and −50 millivolts it then causes a sudden conformational change in the activation gate, flipping it all the way to the open position.
During this activated state, sodium ions can pour inward through the channel, increasing the sodium permeability of the membrane as much as 500- to 5000-fold.
Inactivation of the Sodium Channel
The same increase in voltage that opens the activation gate also closes the inactivation gate. The inactivation gate, however, closes a few 10,000ths of a second after the activation gate opens. That is, the conformational
change that flips the inactivation gate to the closed state is a slower process than the conformational change that
opens the activation gate. Therefore, after the sodium channel has remained open for a few 10,000ths of a second, the inactivation gate closes and sodium ions no longer can pour to the inside of the membrane. At this point, the membrane potential begins to return toward the resting membrane state, which is the repolarization process.
Another important characteristic of the sodium channel inactivation process is that the inactivation gate will not reopen until the membrane potential returns to or near the original resting membrane potential level.
Voltage-Gated Potassium Channel
and Its Activation
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. When the membrane potential rises from −90 millivolts toward zero, this
voltage change causes a conformational opening of the gate and allows increased potassium diffusion outward
through the channel.
Thus, the decrease in sodium entry to the cell and the simultaneous increase in potassium exit from the cell combine to speed the repolarization process, leading to full recovery of the resting membrane potential within another few 10,000ths of a second.
INITIATION OF THE ACTION POTENTIAL
A Positive-Feedback Cycle Opens the Sodium Channels
First, as long as the membrane of the nerve fiber remains undisturbed, no action potential occurs in the
normal nerve. However, if any event causes enough initial rise in the membrane potential from −90 millivolts toward
the zero level, the rising voltage will cause many voltage-gated sodium channels to begin opening. This occurrence
allows rapid inflow of sodium ions, which causes a further rise in the membrane potential, thus opening still
more voltage-gated sodium channels and allowing more streaming of sodium ions to the interior of the fiber. This
process is a positive-feedback cycle that, once the feedback is strong enough, continues until all the voltage-gated sodium channels have become activated (opened). Then, within another fraction of a millisecond, the rising
membrane potential causes closure of the sodium channels and opening of potassium channels, and the action
potential soon terminates.
The threshold for Initiation of the Action Potential.
An action potential will not occur until the initial rise in membrane potential is great enough to create the positive
feedback described in the preceding paragraph. This occurs when the number of sodium ions entering the fiber becomes greater than the number of potassium ions leaving the fiber. A sudden rise in membrane potential of
15 to 30 millivolts are usually required. Therefore, a sudden increase in the membrane potential in a large nerve fiber
from −90 millivolts up to about −65 millivolts usually causes the explosive development of an action potential.
This level of −65 millivolts is said to be the threshold for stimulation.
PROPAGATION OF THE ACTION POTENTIAL
Action potential elicited at any one point on an excitable membrane usually excites adjacent portions
of the membrane, resulting in propagation of the action potential along the membrane. When the nerve excited it suddenly develops increased permeability to sodium
positive electrical charges are carried by the inward-diffusing sodium ions through the depolarized
membrane and then for several millimeters in both directions along with the core of the axon. sodium channels in the new areas immediately open,
These newly depolarized areas produce still more local circuits of current flow farther
along the membrane, causing progressively more and more depolarization. Thus, the depolarization process
travels along the entire length of the fiber. This transmission of the depolarization process along a nerve or muscle
fiber is called a nerve or muscle impulse.
Direction of Propagation
The excitable membrane has no single direction of propagation, but the action potential travels in all directions away from the stimulus even along all branches of a nerve fiber until the entire membrane has become depolarized.
Once an action potential has been elicited at any point on the membrane of a normal
fiber, the depolarization process travels over the entire membrane if conditions are right, but it does not travel at
all if conditions are not right. This principle is called the all-or-nothing principle, and it applies to all normal excitable tissues. Occasionally, the action potential reaches a point on the membrane at which it does not generate
sufficient voltage to stimulate the next area of the membrane. When this situation occurs, the spread of depolarization stops. Therefore, for continued propagation of an impulse to occur, the ratio of action potential to threshold
for excitation must at all times be greater than 1. This “greater than 1” requirement is called the safety factor for
RE-ESTABLISHING SODIUM AND POTASSIUM IONIC GRADIENTS AFTER ACTION POTENTIALS ARE
COMPLETED—IMPORTANCE OF ENERGY METABOLISM
The transmission of each action potential along a nerve fiber reduces slightly the concentration differences of sodium and potassium inside and outside the membrane. For a single action potential, this effect is so minute that it cannot be measured. Indeed, 100,000 to 50 million impulses can be transmitted by large nerve fibers before the concentration differences reach the point that action potential conduction ceases. Even so, with time, it becomes necessary to re-establish the sodium and potassium membrane concentration differences, which are achieved by the action of the Na+ K+pump in the same way as described previously for the original establishment of the resting potential. This pump requires energy for operation, this “recharging” of the nerve fiber is an active metabolic process, using energy derived from the adenosine triphosphate energy system of the cell. Figure 5-12 shows that the nerve fiber produces increased heat during recharging, which is a measure of energy expenditure when the nerve impulse frequency increases. A special feature of the Na+ K+ ATPase pump is that its degree of activity is strongly stimulated when excess sodium ions accumulate inside the cell membrane. In fact, the pumping activity increases approximately in proportion to the third power of this intracellular sodium concentration. As the internal sodium concentration rises from 10 to 20 mEq/L, the
activity of the pump does not merely double but increases about eightfold. Therefore, it is easy to understand how
the “recharging” process of the nerve fiber can be set rapidly into motion whenever the concentration differences of sodium and potassium ions across the membrane begin to “run down.”
PLATEAU IN SOME ACTION POTENTIALS
In some instances, the excited membrane does not repolarize immediately after depolarization; instead, the
potential remains on a plateau near the peak of the spike potential for many milliseconds, and only then does repolarization begin.
This type of action potential occurs in heart muscle fibers, where the plateau lasts for as long as 0.2 to 0.3 seconds and causes contraction of the heart muscle to last for this same long period.The cause of the plateau is a combination of several factors. First, in heart muscle, two types of channels contribute to the depolarization process:
(1) the usual voltage-activated sodium channels called fast channels, and
(2) voltage-activated calcium-sodium channels (L-type calcium channels), which are slow to open and therefore are called slow channels. The opening of fast channels causes the spike portion of the action potential, whereas the
prolonged opening of the slow calcium-sodium channels mainly allows calcium ions to enter the fiber, which is
largely responsible for the plateau portion of the action potential. A second factor that may be partly responsible for theplateau is that the voltage-gated potassium channels areslower to open than usual, often not opening much until
the end of the plateau. This factor delays the return of the membrane potential toward its normal negative value of
−80 to −90 millivolts. The plateau ends when the calcium sodium channels close and permeability to potassium