CAPON overexpression in isolated ventricular myocytes accelerates cardiac repolarization by interacting with NOS1 and inhibiting the L-type calcium channel.
Does CAPON overexpression modulate cardiac repolarization in isolated ventricular myocytes?
CAPON interacts with NOS1 to accelerate cardiac repolarization by inhibiting L-type calcium channels, providing a mechanistic rationale for its association with QT interval variations.
Congenital long- or short-QT syndrome may lead to life-threatening ventricular tachycardia and sudden cardiac death. Apart from the rare disease-causing mutations, common genetic variants in CAPON, a neuronal nitric oxide synthase (NOS1) regulator, have recently been associated with QT interval variations in a human whole-genome association study. CAPON had been unsuspected of playing a role in cardiac repolarization; indeed, its physiological role in the heart (if any) is unknown. To define the biological effects of CAPON in the heart, we investigated endogenous CAPON protein expression and protein-protein interactions in the heart and performed electrophysiological studies in isolated ventricular myocytes with and without CAPON overexpression. We find that CAPON protein is expressed in the heart and interacts with NOS1 to accelerate cardiac repolarization by inhibition of L-type calcium channel. Our findings provide a rationale for the association of CAPON gene variants with extremes of the QT interval in human populations.
Chang et al. (2008) studied QT interval variations. CAPON overexpression vs. Without CAPON overexpression was evaluated on Cardiac repolarization. CAPON overexpression in isolated ventricular myocytes accelerates cardiac repolarization by interacting with NOS1 and inhibiting the L-type calcium channel.