CAPON modulates cardiac repolarization via neuronal nitric oxide synthase signaling in the heart

Kuan Cheng Chang, Andreas S. Barth, Tetsuo Sasano, Eddy Kizana, Yuji Kashiwakura, Yiqiang Zhang, D. Brian Foster, Eduardo Marbán

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4477-4482
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number11
DOIs
StatePublished - Mar 18 2008

Keywords

  • Cardiac electrophysiology
  • NOS1
  • QT interval

ASJC Scopus subject areas

  • General

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