Rafael Mejia-Alvarez, M.D., Ph.D.

My research focuses on understanding the mechanisms that govern Ca²⁺ release from intracellular stores, namely the sarcoplasmic and endoplasmic reticulum (SR and ER), in excitable cells. Specifically, I seek to define how Ca²⁺ release units, formed by either ryanodine receptors (RyRs) or inositol 1,4,5-trisphosphate receptors (IP₃Rs), operate under the control of membrane Ca²⁺ channels (DHPRs) and/or receptor-activated signaling pathways.

To address these questions, the functional properties of Ca²⁺ release events are investigated at the global (transients and waves), local (sparks and puffs), and molecular (single-channel) levels. These findings are interpreted in the context of cardiac excitation-contraction coupling and arrhythmogenic intracellular channelopathies.

These studies employ a multidisciplinary experimental approach that integrates immunocytochemistry, electrophysiology, and advanced fluorescence microscopy, including line-scan confocal imaging of Ca²⁺ signals in single cells and pulsed local-field fluorescence imaging in intact, beating hearts. My long-term goal is to elucidate the molecular mechanisms underlying Ca²⁺ signaling in excitable cells and, in doing so, provide new insights into the local regulation of intracellular Ca²⁺ release channels.