Abstract
Cardiac excitation-contraction (EC) coupling, which links plasma membrane depolarization to activation of cardiomyocyte contraction, occurs at dyads, the nanoscopic microdomains formed by apposition of transverse (T)-tubules and junctional sarcoplasmic reticulum (jSR). In a dyadic junction, EC coupling occurs through Ca(2+)-induced Ca(2+) release. Membrane depolarization opens voltage-gated L-type Ca(2+) channels (LTCCs) in the T-tubule. The resulting influx of extracellular Ca(2+) into the dyadic cleft opens Ca(2+) release channels known as ryanodine receptors (RYRs) in the jSR, leading to the rapid increase in cytosolic Ca(2+) that triggers sarcomere contraction. The efficacy of LTCC-RYR communication greatly affects a myriad of downstream intracellular signaling events, and it is controlled by many factors, including T-tubule and jSR structure, spatial distribution of ion channels, and regulatory proteins that closely regulate the activities of channels within dyads. Alterations in dyad architecture and/or channel activity are seen in many types of heart disease. This review will focus on the current knowledge regarding cardiac dyad structure and function, their alterations in heart failure, and new approaches to study the composition and function of dyads.