|Julio A. Copello, Ph.D.
Excitation-Contraction Coupling in Cardiac and Skeletal Muscle
Excitation-Contraction Coupling in Cardiac and Skeletal Muscle. In striated muscles, large and transient increase in cytosolic calcium is induced by excitatory processes. Calcium then starts the contractile event as required for the heartbeat and for the skeletal muscle twitch. Our goal is to understand this process of “excitation-contraction (EC) coupling” both in health and diseases. Our methodological approach combines biochemistry, electrophysiology and calcium imaging. In cardiac and intracellular reticular meshwork of vesicular and tubular calcium intracellular stores (the sarcoplasmic reticulum [SR]). On the surface of the SR vesicles there are coordinated arrays of calcium channel molecules named ryanodine receptors (as they tightly bind the alkaloid ryanodine) or foot structures (as seen by electron microscopy). We study how these intracellular calciums release channels, (RyR) synchronously activate and rapidly mobilize large amounts of calcium. We also want to understand the mechanisms of communication between RyRs in SR intracellular stores and I-type calcium channels (dihydropyridine receptors, DHPR) in t-tubular invaginations of plasma membranes. It has been known for decades that DHPR triggers RyR activation during the excitatory process. Yet, many details of these DHPR-RyR interactions are not well known. More recently, we have detected that DHPR also represses RyR in resting cells. Understanding his process is important as its failure could originate the enhanced SR-calcium leak found in various muscle and heart diseases.