Pore stability and gating in voltage-activated calcium channels.
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.
Institute of Pharmacology and Toxicology, University of Vienna, Vienna, Austria. steffen.hering@univie.ac.at
Steffen
S
Hering
Stansilav
S
Beyl
Anna
A
Stary
Michaela
M
Kudrnac
Annette
A
Hohaus
H Robert
HR
Guy
Eugen
E
Timin
D000818:Animals; D015220:Calcium Channels / Q000737:chemistry* / Q000502:physiology*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D015640:Ion Channel Gating; D008564:Membrane Potentials; D055550:Protein Stability
D015220:Calcium Channels