Ionic channels in excitable membranes. Current problems and biophysical approaches.

Ionic channels are gated aqueous pores whose conformational changes are driven by the electric field in the membrane. Gating may be studied by three electrical methods: ionic current transients, ionic current fluctuations, and "gating current," and probably occurs through a series of conformational changes in the channel leading to an all-or-nothing opening of the pore. When the potential is held constant, the gating steps come to equilibrium rather than reaching an energy-dissipating, cyclic steady state. The kinetic models now in use eventually need to be changed to correct disagreements with several recent studies. Diffusion of ions through open channels is very fast but involves many interactions of ions, pore, and solvent that lead to ionic selectivity, saturation, block, and flux coupling. Our description of the ionic fluxes can be improved by abandoning continuum models in favor of more structured ones. Problems to be solved include determining how many ions occupy a channel at once and what to be solved include determining how many ions occupy a channel at once and what kind of energy barriers they must cross in traversing the membrane. Ultimately we will need to know the chemical structure of the whole system to understand how it functions.