The individual N- and C-lobes of calmodulin tether to the Cav1.2 channel and rescue the channel activity from run-down in ventricular myocytes of guinea-pig heart

The present study examined the binding of the individual N- and C-lobes of calmodulin (CaM) to Cav1.2 at different Ca2+ concentration ([Ca2+]) from ≈ free to 2 mM, and found that they may bind to Cav1.2 Ca2+-dependently. In particular, using the patch-clamp technique, we confirmed that the N- or C-lobes can rescue the basal activity of Cav1.2 from run-down, demonstrating the functional relevance of the individual lobes. The data imply that at resting [Ca2+], CaM may tether to the channel with its single lobe, leading to multiple CaM molecule binding to increase the grade of Ca2+-dependent regulation of Cav1.2.