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The moving parts of voltage-gated ion channels
Published online by Cambridge University Press: 01 August 1998
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 240
1.1 Basic structure of voltage-activated channels 241
1.2 What are the physical motions of the channel protein during gating? 243
1.3 Gating involves several distinct mechanisms of activation and inactivation 246
2. ACTIVATION GATING 246
2.1 Early evidence for an activation gate at the intracellular mouth 247
2.1.1 Open channel blockade 247
2.1.2 The ‘ foot-in-the-door’ effect 249
2.1.3 Trapping of blockers behind closed activation gates 249
2.2 Site-directed mutagenesis and the difficulty of inferring structural roles from functional effects 250
2.3 State-dependent cysteine modification as a reporter of position and motion 251
2.4 Localization of activation gating 254
2.4.1 The trapping cavity 254
2.4.2 The activation gate 255
2.4.3 Is there more than one site of activation gating? 258
3. INACTIVATION GATING 259
3.1 Ball-and-chain (N-type) inactivation 261
3.1.1 Nature of the ‘ball’ – a tethered blocking particle 262
3.1.2 The ball receptor 263
3.1.3 The chain 264
3.1.4 Variations on the N-type inactivation theme: multiple balls, foreign balls, anti-balls 265
3.2 C-type inactivation 266
3.2.1 C-type inactivation and the outer mouth of the K+channel 266
3.2.2 The selectivity filter participates in C-type inactivation 267
3.2.3 A consistent structural picture of C-type inactivation 269
3.3 By what mechanism do other voltage-gated channels inactivate? 272
4. THE VOLTAGE SENSOR 273
4.1 Quantitative principles of voltage-dependent gating 276
4.2 S4 (and its neighbours) as the principal voltage sensor 277
4.2.1 Mutational effects on voltage-dependence and charge movement 277
4.2.2 Evidence for the translocation of S4 279
4.2.3 Real-time monitoring of S4motion by fluorescence 282
4.3 Coupling between the voltage sensor and gating 283
5. CONCLUSION 284
6. ACKNOWLEDGEMENTS 287
7. REFERENCES 287
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- Review Article
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- © 1998 Cambridge University Press
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