The Journal of General Physiology
Avanti Polar Lipids
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Published online Dec 28 2004. doi:10.1085/jgp.200409194
The Rockefeller University Press, 0022-1295 $8.00
JGP, Volume 125, Number 1, 71-80
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Coupling of Voltage Sensing to Channel Opening Reflects Intrasubunit Interactions in Kv Channels

Alain J. Labro, Adam L. Raes, and Dirk J. Snyders

Laboratory for Molecular Biophysics, Physiology, and Pharmacology, Department of Biomedical Sciences, University of Antwerp, Antwerp 2610, Belgium

Correspondence to Dirk J. Snyders: dirk.snyders{at}ua.ac.be

Voltage-gated K+ channels play a central role in the modulation of excitability. In these channels, the voltage-dependent movement of the voltage sensor (primarily S4) is coupled to the (S6) gate that opens the permeation pathway. Because of the tetrameric structure, such coupling could occur within each subunit or between adjacent subunits. To discriminate between these possibilities, we analyzed various combinations of a S4 mutation (R401N) and a S6 mutation (P511G) in hKv1.5, incorporated into tandem constructs to constrain subunit stoichiometry. R401N shifted the voltage dependence of activation to negative potentials while P511G did the opposite. When both mutations were introduced in the same {alpha}-subunit of the tandem, the positive shift of P511G was compensated by the negative shift of R401N. With each mutation in a separate subunit of a tandem, this compensation did not occur. This suggests that for Kv channels, the coupling between voltage sensing and gating reflects primarily an intrasubunit interaction.

Key Words: hKv1.5 • gating • S4 segment • S6 gate • dimers


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