Recent advances in the characterization of epithelial ionic channels.

Physiologists have long recognized the importance of channels in the functioning of neurons and excitable membranes. This brief review has been an attempt to illustrate how channel properties are also essential to an understanding of epithelial transport physiology. Among their more important functions, channels influence membrane potentials and serve as conduits for ion movements. As the need to understand the molecular basis for ion transport continues to develop, it is crucial to be able to distinguish between different channel properties. For example, apparent voltage-dependent properties can arise because of a voltage-dependent gating process, or alternatively, because of a rectification of channel conductance. Voltage-dependent effects can also be only indirect, mediated by changes in cell volume, intracellular ion levels, the levels of secondary intracellular messengers such as Ca2+ (perhaps through voltage-dependent membrane Ca2+ channels), or possibly even by morphological changes. An important area for future research is to differentiate mechanisms which modulate the activity of open channels. For example, a decrease in channel number, a reduction in open-channel conductance or a decline in the probability of channel opening can all underlie changes in macroscopic permeability. The factors which mediate hormonal activation of epithelial channels particularly need to be understood. Specifically, the mechanisms of aldosterone and anti-diuretic hormone activation of apical membrane Na+ channels need to be identified. In conclusion, we are witnessing a new era in epithelial electrophysiology which promises to resolve many issues concerning the cellular regulation of ion transport and open new, unanticipated avenues of inquiry.