Key result
Substitution of two divergent residues in the IQ motif of CaV1.2 with those of CaV1.1 (Y1657H, K1662M) weakened calmodulin binding and eliminated calcium-dependent inactivation.
Conserved sequence differences in the IQ motifs of CaV1.2 and CaV1.1 have a profound effect on calmodulin binding and calcium-dependent inactivation.
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Requires validation in native cardiomyocytes before any therapeutic consideration; leaves open contributions to human channelopathies or drug responses.
Ohrtman et al. (2008) studied this question. Substitution of divergent residues in the IQ motif of CaV1.2 with those of CaV1.1 (Y1657H, K1662M) vs. Wild-type CaV1.2 was evaluated on Calmodulin (CaM) binding and calcium-dependent inactivation. Substitution of two divergent residues in the IQ motif of CaV1.2 with those of CaV1.1 (Y1657H, K1662M) weakened calmodulin binding and eliminated calcium-dependent inactivation.
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