Abstract
During cardiac excitation contraction coupling, the arrival of an action potential at the ventricular myocardium triggers voltage-dependent L-type Ca(2+) (Ca(V)1.2) channels in individual myocytes to open briefly. The level of this Ca(2+) influx tunes the amplitude of Ca(2+)-induced Ca(2+) release from ryanodine receptors (RyR2) on the junctional sarcoplasmic reticulum and thus the magnitude of the elevation in intracellular Ca(2+) concentration and ultimately the downstream contraction. The number and activity of functional Ca(V)1.2 channels at the t-tubule dyads dictates the amplitude of the Ca(2+) influx. Trafficking of these channels and their auxiliary subunits to the cell surface is thus tightly controlled and regulated to ensure adequate sarcolemmal expression to sustain this critical process. To that end, recent discoveries have revealed the existence of internal reservoirs of preformed Ca(V)1.2 channels that can be rapidly mobilized to enhance sarcolemmal expression in times of acute stress when hemodynamic and metabolic demand increases. In this review, we provide an overview of the current thinking on Ca(V)1.2 channel trafficking dynamics in the heart. We highlight the numerous points of control including the biosynthetic pathway, the endosomal recycling pathway, ubiquitination, and lysosomal and proteasomal degradation pathways, and discuss the effects of β-adrenergic and angiotensin receptor signaling cascades on this process.