Zinc controls RyR2 activity during excitation-contraction coupling

Abstract

Cardiac excitation-contraction (EC) coupling is a process which governs contractility of the heart through the controlled release of Ca2+ from the sarcoplasmic reticulum (SR). The type-2 ryanodine receptor (RyR2) is the route through which Ca2+ is released from the SR providing the necessary driving force for cellular contraction. In heart failure, RyR2-channels become abnormally active, or ‘leaky’, and are unable to remain closed during diastole resulting in unwanted irregular contractile and electrical activity1. Defective Zn2+ handling has been shown to contribute to the cellular pathology of certain cardiomyopathies which give rise to impaired contractility including heart failure 2. This is likely a consequence of altered EC coupling as a result of modified RyR2 function. How zinc impacts upon the contractile force and the release of calcium from intracellular stores in heart is not fully understood.