Hypothetical model for the mechanism of action of scoparone against T. cinnabarinus via the CaM-mediated activation of L-VGCC. a At low [Ca2+]i, CaM is mostly in the Ca2+-free form (apoCaM) and interacts with elevated affinity with the PreIQ domain in the C-terminus of L-VGCC, producing basal channel activity. b However, as [Ca2+]i increases, Ca2+-bound CaM (Ca2+/CaM) forms and interacts with elevated affinity with the IQ domain, resulting in CDF. Scoparone activates the CaM-binding site, which is located in the IQ region at the C-terminus of the Ca2+ channel. A further increase in [Ca2+]i promotes the interaction of Ca2+/CaM with PreIQ or the NT region, leading to CDI.