Pore stability and gating in voltage-activated calcium channels
| Autor: | Robert H. Guy, Eugen Timin, Michaela Kudrnac, Steffen Hering, Stanislav Beyl, Anna Stary, Annette Hohaus |
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| Rok vydání: | 2008 |
| Předmět: |
Membrane potential
Voltage-dependent calcium channel Chemistry Protein Stability Calcium channel Biophysics Analytical chemistry Gating Biochemistry Article Membrane Potentials Channel types Animals Humans Sensitivity (control systems) Calcium Channels Hydrophobic and Hydrophilic Interactions Ion Channel Gating Voltage Communication channel |
| Zdroj: | Channels (Austin, Tex.). 2(2) |
| ISSN: | 1933-6969 |
| Popis: | 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 varietys of voltage sensitivities of different channel types was accomplished by shaping pore stability. |
| Databáze: | OpenAIRE |
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