Cardiac Functions of Voltage-Gated Ca2+ Channels: Role of the Pharmacoresistant Type (E-/R-Type) in Cardiac Modulation and Putative Implication in Sudden Unexpected Death in Epilepsy (SUDEP)

Voltage-gated Ca2+ channels (VGCCs) are ubiquitous in excitable cells. These channels play key roles in many physiological events like cardiac regulation/ pacemaker activity due to intracellular Ca2+ transients. In the myocardium, the Cayl subfamily (L-type: C41.2 and C41.3) is the main contributor to excitation contraction coupling and/or pacemaking, whereas the Ca(v)3 subfamily (T-type: Cay3.1 and Cay3.2) is important in rhythmically firing of the cardiac nodal cells. No established cardiac function has been attributed to the Ca(v)2 family (E-/R-type: Ca(v)2.3) despite accumulating evidence of cardiac dysregulation observed upon deletion of the Ca(v)2.3 gene, the only member of this family so far detected in cardiomyocytes. In this review, we summarize the pathophysiological changes observed after ablation of the E-/R-type VGCC and propose a cardiac mechanism of action for this channel. Also, considering the role played by this channel in epilepsy and its reported sensitivity to antiepileptic drugs, a putative involvement of this channel in the cardiac mechanism of sudden unexpected death in epilepsy is also discussed