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Current Topics in Ion Channels

Pore stability and gating in voltage-activated calcium channels

Steffen Hering, Stanislav Beyl, Anna Stary, Michaela Kudrnac, Annette Hohaus, Robert H. Guy and Eugen Timin

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Calcium channel family members activate at different membrane potentials which enables tissue specific calcium entry. Pore mutations affecting this voltage dependence are associated with channelopathies. In this review we analyze the link between voltage sensitivity and corresponding kinetic phenotypes of calcium channel activation. Systematic changes in hydrophobicity in the lower third of S6 segments gradually shift the activation curve thereby determining the voltage sensitivity. Homology modeling suggests that hydrophobic residues that are located in all four S6 segments close to the inner channel mouth might form adhesion points stabilizing the closed gate. Simulation studies support a scenario where voltage sensors and the pore are essentially independent structural units. We speculate that evolution designed the voltage sensing machinery as robust "all-or-non" device while the verity of voltage sensitivities of different channel types was accomplished by shaping pore stability.

Authors

Steffen Hering

University of Vienna

Stanislav Beyl

University of Vienna

Anna Stary

Max Planck Institute for Biophysical Chemistry

Michaela Kudrnac

Universtiy of Vienna

Annette Hohaus

University of Vienna

Robert H. Guy

National Cancer Institute/National Institutes of Health

Eugen Timin

University of Vienna

Purchase article for $19

Subscribe to this journal for $79/year