Research

Ca²⁺ signaling dynamics

The Ca²⁺ signaling system is central to the E-C coupling in cardiomyocytes. During the action potential (AP), the L-type Ca²⁺ channels open and Ca²⁺ enters the cell, which triggers opening of the ryanodine receptors (RyR), which then allows a massive Ca²⁺ release from SR to cause a cytosolic Ca²⁺ transient.  This Ca²⁺-induced Ca²⁺ release is a positive feedback mechanism that governs the Ca²⁺ signaling system. In heathy heart, the Ca²⁺-induced Ca²⁺ release is synchronized through the T-tubule network that gives rise to a uniform Ca²⁺ transient to trigger cell contraction. However, in diseased heart, detubulation causes some RyRs to become decoupled to the L-type Ca channels (called orphan RyRs). The Ca²⁺ released from early opening RyRs can diffuse to neighboring orphan RyRs to release more Ca²⁺, causing regenerative Ca²⁺ waves. The Ca²⁺ waves are spontaneous in nature, which can cause arrhythmogenic electrical activities. We combine experiments with mathematical modeling to study the Ca²⁺ dynamics are important to heart function and arrhythmias.