title: Nitroxyl enhances myocyte Ca2+ transients by exclusively targeting SR Ca2+-cycling.
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 per cent repolarization with AS/HNO, whereas AP duration to 90 per cent 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.
authors.affiliation: Department of Physiology and Cell Biology, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Kohr
authors.forename: Nina
authors.initials: N
authors.lastname: Kaludercic
authors.forename: Carlo G
authors.initials: CG
authors.lastname: Tocchetti
authors.forename: Wei
authors.initials: W
authors.lastname: Dong Gao
authors.forename: David A
authors.initials: DA
authors.lastname: Kass
authors.forename: Paul M L
authors.initials: PM
authors.lastname: Janssen
authors.forename: Nazareno
authors.initials: N
authors.lastname: Paolocci
authors.forename: Mark T
authors.initials: MT
authors.lastname: Ziolo
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D017665:Hydroxyl Radical / Q000494:pharmacology; D008297:Male; D051379:Mice; D009200:Myocardial Contraction / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000187:drug effects*; D009573:Nitrites / Q000494:pharmacology*; D009589:Nitrogen Oxides / Q000494:pharmacology*; D051381:Rats; D012519:Sarcoplasmic Reticulum / Q000187:drug effects*
chemical_list: D009573:Nitrites; D009589:Nitrogen Oxides; C021229:oxyhyponitrite; D017665:Hydroxyl Radical; C039900:nitroxyl; D002118:Calcium