Chemical tools for K(+) channel biology.

Abstract:

:K(+) channels are revered for their universal action of suppressing electrical activity in nerve and muscle, as well as regulating salt and water transport in epithelial tissues involved in metabolism and digestion. These multisubunit membrane-embedded proteins carry out their physiological chore, selectively allowing the passage of potassium across the membrane, in response to changes in membrane voltage and ligand concentration. Elucidating the diverse gating properties of K(+) channels is of great biological interest since their molecular motions provide insight into how these structurally similar proteins function in a wide variety of tissues. Armed with patch clamps, chart recorders, and now high-resolution structures, electrophysiologists have been dipping into the top tray of the chemist's tool box: synthesizing cysteine-modifying agents and organic cations and grinding up insects, spiders, and other vermin to isolate natural products to poke, probe, and prod K(+) channels. Recently, there has been further cross-fertilization between chemists and K(+) channelologists, resulting in greater accessibility to more elaborate synthetic methodologies and screening approaches. In this review, we catalogue the evolution of chemical tools and approaches that have been utilized to elucidate the mechanistic underpinnings of K(+) channel biology.

journal_name

Biochemistry

journal_title

Biochemistry

authors

Ahern CA,Kobertz WR

doi

10.1021/bi8018515

subject

Has Abstract

pub_date

2009-01-27 00:00:00

pages

517-26

issue

3

eissn

0006-2960

issn

1520-4995

pii

10.1021/bi8018515

journal_volume

48

pub_type

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