Discrete membrane surface charge distributions. Effect of fluctuations near individual channels.

Each gating mechanism controlling permeability in a membrane may be influenced by only a few charge binding sites on the membrane surface, so that fluctuations in the occupancy of these sites are important. Tow extreme cases arise. (a) The time scale of these fluctuations is much shorter than the gating time constant. Then the gating mechanisms are subject to a rapidly varying electric field. If the gating in the absence of these fluctuations obeys exponential kinetics, so does the gating in the presence of the fluctuations. Changes in surface charge do not simply shift the gating variable curves on the voltage axis, but also change their shape. Such effects are seen experimentally and cannot be explained in terms of conventional surface charge theory. If the activation curve in the absence of any surface charge binding is symmetric about the half-activation point, when some of the surface charge sites are occupied the activation curve is in general asymmetric. (b) The fluctuations occur much more slowly than the gating reaction. There are several pools of channels present with different time constant and activation curves. Again the activation curve is asymmetric about the half-activation point, and its shape is changed by alterations in the surface charge. The kinetics of gating of the whole population of channels are multiexponential.