FIGURE 5.

A hypothetical model for competitions between CSL and CaM on the Cav1.2 channel. A, at low [Ca²⁺], CaM is mostly in the Ca²⁺-free form (apoCaM) and interacts with the IQ domain in the C terminus (C-term) of the Cav1.2 channel, producing basal channel activity. CSL competes with CaM for the site in the IQ domain. Interaction of CaM with NT, LI-II, or PreIQ is minimal in this condition. B, when [Ca²⁺] is increased, Ca²⁺-bound CaM (Ca²⁺/CaM) is formed and interacts with higher affinity with the IQ domain, resulting in Ca²⁺-dependent facilitation. Further increase in [Ca²⁺] promotes the interaction of Ca²⁺/CaM with NT and/or PreIQ and possibly with LI-II, leading to Ca²⁺-dependent inactivation. CSL does not interact with these regions and therefore does not affect the Ca²⁺-dependent inactivation.