Voltage-gated ion channels are fundamental for electrical signaling in living cells. They are composed of four subunits, each holding six trans-membrane helices, S1-S6. Each subunit contains a voltage-sensor domain, S1-S4, and a pore domain, S5-S6. S4 contains several positively charged amino-acid residues and moves in response to changes in membrane voltage. This movement controls the opening and closing of the channel. The structure of the pore domain is solved and demonstrates principles of channel selectivity. The molecular mechanism of how the voltage sensor regulates the opening of the channel is still under discussion. Several models have been discussed. One of the models is the paddle model where S3b and S4 move together. The second one is the helical-twist where S4 makes a small rotation in order for the channel to open. The third one is the helical-screw model where S4 twists around its axis and moves diagonally towards the extracellular side of the channel.The aim of this PhD project was to study the molecular movement of the voltage sensor in the depolarization-activated…
Contents
INTRODUCTION
Voltage-gated K ion channels
The pore domain
The voltage-sensor domain
The intracellular domains
AIM
METHOD
Molecular biology
Xenopus laevis and its oocyte
Surgery and injection
Electrophysiology
Cysteine modification
Oxaliplatin
RESULTS AND DISCUSSION
Voltage-sensor movement (Papers I and II)
Electrostatic effects of compounds in the extracellular fluid (Papers III and IV)
CONCLUSIONS
ACKNOWLEDGMENTS
REFERENCES
Author: Broomand, Amir
Source: Linkoping University
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