Ionic Mechanisms Underlying The Endplate Potential

How does ACh produce the permeability change responsible for the EPP? In the early 1950s, Bernard Katz and his colleagues proposed that the binding of ACh with receptors on the postjunctional membrane led to a simultaneous increase in Na+ and K+ permeabilities. If a membrane is permeable only to Na+ and K+, then the Goldman-Hodgkin-Katz (GHK) equation is applicable:

where a = PNa/PK. If a = 1 and the K+ and Na+ concentrations on the inside and outside of the cell are substituted into the equation, a membrane potential of about 0 mV is predicted.

Even though the EPP is due to the opening channels that have equal permeability to Na+ and K+, an EPP with a peak value of 0 mV does not occur for two reasons. First, as the muscle membrane depolarizes toward 0 mV, threshold is reached, and an action potential is initiated or triggered and the EPP is obscured. Second, the membrane channels opened by ACh are only a small fraction of the ion channels in the muscle cell. These other channels (not affected by ACh) tend to hold the membrane potential at the resting potential and prevent the membrane potential from reaching the 0-mV level. (When the EPP triggers an action potential, a potential more positive than 0 mV is reached, but this is a reflection of the ionic mechanisms underlying the action potential and not the ionic mechanisms underlying the EPP.)

During the past 15 years, considerable evidence has accumulated about the molecular events associated with the actions of ACh. Using patch recording techniques (Fig. 11), it has been possible to measure the ionic current flowing through single channels opened by ACh. When the micropipette contains normal saline without ACh, no electrical changes are observed. However, when ACh is added to the electrode, small, step-like fluctuations are observed which are the result of ions flowing through specific membrane channels that are opened by ACh. The electrical events associated with the opening of a single channel are extremely small and, as a result, any single channel makes a small contribution to the normal EPP.

As a result of these patch recording techniques, three general conclusions can be drawn. First, ACh causes the opening of individual ionic channels (for a channel to open, two molecules of ACh must bind to the receptor). Second, when an ACh-sensitive channel opens, it does so in an all-or-nothing fashion. Increasing the concentration of ACh in the patch microelectrode does not increase the permeability of the channel; rather, it increases its probability of opening. And, finally, when a larger region of the muscle, and thus more than one channel, is exposed to ACh the net permeability is larger because more individual channels are opened, each in their characteristic all-or-nothing fashion. It is this summation of the permeability of many individual open channels that gives rise to the normal EPP. The properties of ACh-sensitive channels and voltage-sensitive Na+ channels are similar in that both channels open in an all-or-nothing fashion and, as a result, the macroscopic effects that are recorded are due to the summation of many individual open ion channels.

A Without ACh

Patch Electrode

ACh sensitive channels

Ionic Current

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