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Structure, Function, and Modification of the Voltage Sensor in Voltage-Gated Ion Channels

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Abstract

Voltage-gated ion channels are crucial for both neuronal and cardiac excitability. Decades of research have begun to unravel the intriguing machinery behind voltage sensitivity. Although the details regarding the arrangement and movement in the voltage-sensor domain are still debated, consensus is slowly emerging. There are three competing conceptual models: the helical-screw, the transporter, and the paddle model. In this review we explore the structure of the activated voltage-sensor domain based on the recent X-ray structure of a chimera between Kv1.2 and Kv2.1. We also present a model for the closed state. From this we conclude that upon depolarization the voltage sensor S4 moves ~13 Å outwards and rotates ~180°, thus consistent with the helical-screw model. S4 also moves relative to S3b which is not consistent with the paddle model. One interesting feature of the voltage sensor is that it partially faces the lipid bilayer and therefore can interact both with the membrane itself and with physiological and pharmacological molecules reaching the channel from the membrane. This type of channel modulation is discussed together with other mechanisms for how voltage-sensitivity is modified. Small effects on voltage-sensitivity can have profound effects on excitability. Therefore, medical drugs designed to alter the voltage dependence offer an interesting way to regulate excitability.

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Acknowledgement

We thank Dr. Bohdan Olaf Sklepkovych (Strategic Communications Grants Office, Linköping University) for linguistic advice. This study was supported by grants from the Swedish Research Council, Linköping University, the County Council of Östergötland, and the Swedish Heart-Lung Foundation.

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  1. Department of Clinical and Experimental Medicine, Division of Cell Biology, Linköping University, SE-581 85, Linköping, Sweden

    Sara I. Börjesson & Fredrik Elinder

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  1. Sara I. Börjesson
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  2. Fredrik Elinder
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Correspondence to Fredrik Elinder.

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Börjesson, S.I., Elinder, F. Structure, Function, and Modification of the Voltage Sensor in Voltage-Gated Ion Channels. Cell Biochem Biophys 52, 149–174 (2008). https://doi.org/10.1007/s12013-008-9032-5

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