title: Prolonged Action Potential and After depolarizations Are Not due to Changes in Potassium Currents in NOS3 Knockout Ventricular Myocytes.
abstract: Ventricular myocytes deficient in endothelial nitric oxide synthase (NOS3(-/-)) exhibit prolonged action potential (AP) duration and enhanced spontaneous activity (early and delayed afterdepolarizations) during β-adrenergic (β-AR) stimulation. Studies have shown that nitric oxide is able to regulate various K(+) channels. Our objective was to examine if NOS3(-/-) myocytes had altered K(+) currents. APs, transient outward (I(to)), sustained (I(Ksus)), and inward rectifier (I(K1)) K(+) currents were measured in NOS3(-/-) and wild-type (WT) myocytes. During β-AR stimulation, AP duration (measured as 90% repolarization-APD(90)) was prolonged in NOS3(-/-) compared to WT myocytes. Nevertheless, we did not observe differences in I(to), I(Ksus), or I(K1) between WT and NOS3(-/-) myocytes. Our previous work showed that NOS3(-/-) myocytes had a greater Ca(2+) influx via L-type Ca(2+) channels with β-AR stimulation. Thus, we measured β-AR-stimulated SR Ca(2+) load and found a greater increase in NOS3(-/-) versus WT myocytes. Hence, our data suggest that the prolonged AP in NOS3(-/-) myocytes is not due to changes in I(to), I(Ksus), or I(K1). Furthermore, the increase in spontaneous activity in NOS3(-/-) myocytes may be due to a greater increase in SR Ca(2+) load. This may have important implications for heart failure patients, where arrhythmias are increased and NOS3 expression is decreased.
authors.affiliation: Department of Physiology and Cell Biology, The Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43221, USA.
authors.forename: Honglan
authors.initials: H
authors.lastname: Wang
authors.forename: Ingrid M
authors.initials: IM
authors.lastname: Bonilla
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.forename: Quanhua
authors.initials: Q
authors.lastname: He
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Kohr
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Carnes
authors.forename: Mark T
authors.initials: MT
authors.lastname: Ziolo