Inherited Ventricular Arrhythmias: The Role of the Multi-Subunit Structure of the L-Type Calcium Channel Complex.

The normal heartbeat is conditioned by transient increases in the intracellular free Ca ²⁺ concentration. Ca ²⁺ influx in cardiomyocytes is regulated by the activity of the heteromeric L-type voltage-activated Ca _V 1.2 channel. A complex network of interactions between the different proteins forming the ion channel supports the kinetics and the activation gating of the Ca ²⁺ influx. Alterations in the biophysical and biochemical properties or in the biogenesis in any of these proteins can lead to serious disturbances in the cardiac rhythm. The multi-subunit nature of the channel complex is better comprehended by examining the high-resolution three-dimensional structure of the closely related Ca _V 1.1 channel. The architectural map identifies precise interaction loci between the different subunits and paves the way for elucidating the mechanistic basis for the regulation of Ca ²⁺ balance in cardiac myocytes under physiological and pathological conditions.