Strategies for studying permeation at voltage-gated ion channels

Abstract

Voltage-dependent ion channels are presently thought to consist of several distinct functional regions: (a) activation gates, (b) inactivation gates, and permeation pathways. This chapter focuses on permeation pathways and may spur new ideas about experiments that use site-directed mutagenesis to probe the ion conduction pathway. Some hubris is required to attempt a survey of this field since individual families -- K^+, Na^+, or Ca^(2+) -- have been reviewed in detail (15, 68, 115, 127). My unified treatment is motivated by the structural similarity suggested by recent cDNA sequencing data on this group (see, for instance, 24). There have been many excellent previous treatments of ion channel permeation (6, 15, 34, 35, 51, 53, 68, 73, 74, 115, 127).