Membrane excitation through voltage-induced aggregation of channel precursors.

Electrically excitable lipid bilayers show the same voltage-dependent kinetics as nerve and other excitable cells. In the bilayers the gating process involves the voltage-dependent insertion of channel-forming molecules into the hydrocarbon region and their subsequent aggregation by lateral diffusion into an open "barrel stave channel." This process can account quantitatively for the classical Hodgkin-Huxley kinetics including inactivation as well as for certain kinetic features that lie outside the Hodgkin-Huxley domain. The multi- and single-channel kinetics suggest that both the insertion and the aggregation reate constants are voltage-dependent, and it is argued that a voltage-induced lateral phase separation between the lipids and the channel-forming molecules increases the local concentration of channel precursors and their aggregation rates. Because the observed aggregation rates are faster than those calculated from an upper limit of the diffusion constants and the known average concentration in the lipid phase, it is likely that the channel-formers preaggregate at the membrane surface. The structural characteristics of the channel-formers and the evidence supporting a similar excitation mechanism in nerve are discussed.