TOWARD A MOLECULAR UNDERSTANDING OF VOLTAGE-GATED POTASSIUM CHANNELS

Many different types of potassium (K+) channels exist and they play a central role in the fine tuning of excitability properties. Of the distinct subpopulations of K+ channels expressed in different cells, voltage-gated K+ channels have been studied most thoroughly at a molecular level. Over the last few years, the joint application of recombinant DNA technology together with electrophysiology, such as the voltage clamp and the patch clamp techniques, has produced a wealth of information. We have begun to unravel the genetic basis of ion channel diversity. In particular, the Xenopus oocyte expression system has turned out to be of enormous experimental value. Oocytes microinjected with "cloned" mRNA have been used to gain insight into biophysical and pharmacologic properties of voltage-gated K+, Na+, and Ca2+ channels. Here, we wilt review our understanding of K+ channel diversity based upon the fact that ion channels are encoded as a large multigene family. We have caught a first glimpse at possible molecular mechanisms underlying several biophysical properties characteristic for voltage-gated ion channels: voltage dependence of activation and inactivation, and ion permeation and selectivity. We will discuss molecular mechanisms of K+ channel activation and inactivation. We will also describe experiments that led to the identification of the "pore region," and we will present a model of a potassium selective ion channel pore.