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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
volume 2 | issue 2
March/April 2008Pages: 61 - 69
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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






