Direct Modulation of RyR2 Leading to a TRICky Ca 2+ Balance

GONANO, LUIS A.; VILA PETROFF, MARTIN

CIRCULATION RESEARCH

LIPPINCOTT WILLIAMS & WILKINS

Año: 2020 vol. 126 p. 436 - 438

0009-7330

A central point in heart research is to understand themechanisms behind Ca2+ handling and to find alternativesto correct defective Ca2+ cycling associatedwith heart failure and arrhythmias. In cardiac myocytes,entry of Ca2+ occurs through L-type Ca2+ channels andmediates the opening of RyR2 channels allowing systolicmovement of Ca2+ from the sarcoplasmic reticulum(SR) to the cytosol. In addition, SR Ca2+ release occursrandomly due to RyR2 opening in response to a combinationof factors that favor (luminal and cytosolic Ca2+,ATP, posttranslational modifications; gain-of-functionmutations or drugs) or preclude it (Mg2+, FKBPs, loss-offunctionmutations or drugs). Due to its dependence onluminal SR Ca2+, the concept of store overload?inducedSR Ca2+ release (SOICR) has emerged, and the capabilityof these events to generate delayed afterdepolarizationsand arrhythmias is widely accepted.1 Thus, understandingthe mechanisms that regulate SR Ca2+ release andits capacity to promote SOICR is of critical importance.