Abstract
Ion channels, like many other proteins, have moving parts that perform useful
functions. The channel proteins contain an aqueous, ion-selective pore that
crosses the plasma membrane, and they use a number of distinct ‘gating’
mechanisms to open and close this pore in response to biological stimuli such as
the binding of a ligand or a change in the transmembrane voltage.This review is written at a watershed in our understanding of ion channels.1. INTRODUCTION 2401.1 Basic structure of voltage-activated channels 2411.2 What are the physical motions of the channel protein during gating? 2431.3 Gating involves several distinct mechanisms of activation and inactivation 2462. ACTIVATION GATING 2462.1 Early evidence for an activation gate at the intracellular mouth 2472.1.1 Open channel blockade 2472.1.2 The ‘ foot-in-the-door’ effect 2492.1.3 Trapping of blockers behind closed activation gates 2492.2 Site-directed mutagenesis and the difficulty of inferring structural roles from functional effects 2502.3 State-dependent cysteine modification as a reporter of position and motion 2512.4 Localization of activation gating 2542.4.1 The trapping cavity 2542.4.2 The activation gate 2552.4.3 Is there more than one site of activation gating? 2583. INACTIVATION GATING 2593.1 Ball-and-chain (N-type) inactivation 2613.1.1 Nature of the ‘ball’ – a tethered blocking particle 2623.1.2 The ball receptor 2633.1.3 The chain 2643.1.4 Variations on the N-type inactivation theme: multiple balls, foreign balls, anti-balls 2653.2 C-type inactivation 2663.2.1 C-type inactivation and the outer mouth of the K+channel 2663.2.2 The selectivity filter participates in C-type inactivation 2673.2.3 A consistent structural picture of C-type inactivation 2693.3 By what mechanism do other voltage-gated channels inactivate? 2724. THE VOLTAGE SENSOR 2734.1 Quantitative principles of voltage-dependent gating 2764.2 S4 (and its neighbours) as the principal voltage sensor 2774.2.1 Mutational effects on voltage-dependence and charge movement 2774.2.2 Evidence for the translocation of S4 2794.2.3 Real-time monitoring of S4motion by fluorescence 2824.3 Coupling between the voltage sensor and gating 2835. CONCLUSION 2846. ACKNOWLEDGEMENTS 2877. REFERENCES 287
Publisher
Cambridge University Press (CUP)
Cited by
411 articles.
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