Individual Acetylcholine Receptor-Channels Conduct All-or-None Currents
What are the properties of the ACh receptor-channels that produce the inward current that generates the depolarizing end-plate potential? Which ions move through the channels to produce this inward current? And what does the current carried by a single Ach receptor-channel look like?
In 1976, Erwin Neher and Bert Sakmann obtained key insights into the biophysical nature of ACh receptor- channel function from recordings of the current conducted by single ACh receptor-channels in skeletal muscle cells, the unitary or elementary current. They found that the opening of an individual channel generates a very small rectangular step of ionic current (Figure 12–7A). At a given resting potential, each channel opening generates the same-size current pulse. At −90 mV, the current steps are approximately −2.7 pA in amplitude. Although this is a very small current, it corresponds to a flow of approximately 17 million ions per second!
Whereas the amplitude of the current through a single ACh receptor-channel is constant for every opening, the duration of each opening and the time between openings vary considerably. These variations occur because channel openings and closings are stochastic; they obey the same statistical law that describes the exponential time course of radioactive decay. Because channels and ACh undergo random thermal motions and fluctuations, it is impossible to predict exactly how long it will take any one channel to bind ACh or how long that channel will stay open before the ACh dissociates and the channel closes. However, the average length of time a particular type of channel stays open is a well-defined property of that channel, just as the half-life of radioactive decay is an invariant property of a particular isotope. The mean open time for ACh receptor-channels is approximately 1 ms. Thus, each channel opening permits the movement of approximately 17,000 ions. Once a channel closes, the ACh molecules dissociate and the channel remains closed until it binds ACh again.