Physicochemical properties of pore residues predict activation gating of Ca V1.2: a correlation mutation analysis.

ABSTRACT: Single point mutations in pore-forming S6 segments of calcium channels may transform a high-voltage-activated into a low-voltage-activated channel, and resulting disturbances in calcium entry may cause channelopathies (Hemara-Wahanui et al., Proc Natl Acad Sci U S A 102(21):7553-7558, 16). Here we ask the question how physicochemical properties of amino acid residues in gating-sensitive positions on S6 segments determine the threshold of channel activation of Ca(V)1.2. Leucine in segment IS6 (L434) and a newly identified activation determinant in segment IIIS6 (G1193) were mutated to a variety of amino acids. The induced leftward shifts of the activation curves and decelerated current activation and deactivation suggest a destabilization of the closed and a stabilisation of the open channe

SUBMITTER: Beyl S 

PROVIDER: S-EPMC3016219 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature