Sodium channel gating: models, mimics, and modifiers.

Abstract

Springing from work utilizing numerous preparations and varied bio­ chemical and electrophysiological approaches, a small flood of articles, reviewing diverse studies on sodium channels, has appeared in the last few years (6, 22, 29, 3 1, 37, 77, 138, 139, 170, 174). Rapidly converging lines of work employ techniques for isolation of channel receptor proteins (13, 37, 139), voltage clamp studies of cellular preparations in which channels are modified by group-specific chemical reagents (29), reconstitution of functional channels into lipid vesicles (101, 170, 172), measurements of intramembrane charge movement (3, 6, 22), and treatment by various drugs that modify or mimic physiological sodium channel gating (174). The patch clamp technique (79, 121, 122) has recently made possible the recording of single sodium channel currents in a variety of preparations (65, 89, 90, 160). While much detailed work remains to be done, all of the elements required to assemble a complete description of sodium channel gating, from the response of macromolecular intramembrane charges to a change in membrane field, through the opening and closing of single channels, to the generation of time-variant, voltage-dependent macroscopic currents across the membrane, are now experimentally accessible. The culminating physiological description will require the gathering of all these elements from a single preparation, and their integration into a quantitatively accurate picture.