Nitroxyl enhances myocyte Ca2+ transients by exclusively targeting SR Ca2+-cycling

Mark J. Kohr, Nina Kaludercic, Carlo G. Tocchetti, Wei Dong Gao, David A. Kass, Paul M.L. Janssen, Nazareno Paolocci, Mark T. Ziolo

Research output: Contribution to journalArticlepeer-review

Abstract

Nitroxyl (HNO), the 1-electron reduction product of nitric oxide, improves myocardial contraction in normal and failing hearts. Here we test whether the HNO donor Angeli's salt (AS) will change myocyte action potential (AP) waveform by altering the L-type Ca2+ current (ICa) and contrast the contractile effects of HNO with that of the hydroxyl radical (.OH) and nitrite (NO2-), two potential breakdown products of AS. We confirmed the positive effect of AS/HNO on basal cardiomyocyte function, as opposed to the detrimental effect of.OH and the negligible effect of NO2-. Upon examination of the myocyte AP, we observed no change in resting membrane potential or AP duration to 20% repolarization with AS/HNO, whereas AP duration to 90% repolarization was slightly prolonged. However, perfusion with AS/HNO did not elicit a change in basal ICa, but did hasten ICa inactivation. Upon further examination of the SR, the AS/HNO-induced increase in cardiomyocyte Ca2+ transients was abolished with inhibition of SR Ca2+-cycling. Therefore, the HNO-induced increase in Ca2+ transients results exclusively from changes in SR Ca2+-cycling, and not from ICa.

Original languageEnglish (US)
Pages (from-to)614-626
Number of pages13
JournalFrontiers in Bioscience - Elite
Volume2 E
Issue number2
StatePublished - Jan 1 2010

Keywords

  • Action potential
  • Cardiomyocyte
  • Electrophysiology
  • Excitation-contraction coupling
  • Heart failure
  • L-type Ca current
  • Thapsigargin

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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