Expression and roles of Cav1.3 (α1D) L-Type Ca2+ Channel in atrioventricular node automaticity

Atrioventricular node (AV node) is the hub where electrical input from the atria is propagated and conveyed to the ventricles. Despite its strategic position and role in governing impulse conduction between atria and ventricles, there is paucity of data regarding the contribution of specific ion channels to the function of the AV node. Here, we examined the roles of Ca_v1.3 L-type Ca²⁺ channel in AV node by taking advantage of a mouse model with null mutation of Ca_v1.3 (Ca_v1.3^-/-). Ca_v1.3 null mutant mice show evidence of AV node dysfunction with AV block, suggesting the tissue-specific function of the Ca_v1.3 channel. In keeping with this assertion, we demonstrate that Ca_v1.3 isoform is highly expressed in the isolated AV node cells. Furthermore, AV node isolated from Ca_v1.3 null mutant mice show a significant decrease in the firing frequency of spontaneous action potentials suggesting that Ca_v1.3 L-type Ca²⁺ channel plays significant roles in the automaticity of the AV node. Because of the distinct voltage-dependence of Ca_v1.2 and Ca_v1.3 Ca²⁺ channels, Ca_v1.2 alone does not suffice to maintain normal AV node function. Ca_v1.3 currents activate at more hyperpolarizing voltage compared to Ca_v1.2 currents. Consequently, Ca_v1.2 Ca²⁺ channel cannot functionally substitute for Ca_v1.3 isoform in the AV node of Ca_v1.3 null mutant mice. Thus, our study demonstrates that the distinct biophysical properties of Ca_v1.3 Ca²⁺ channel play critical roles in the firing frequency of AV node tissues.