The Na+-Ca2+ exchanger contributes to β-adrenoceptor mediated positive inotropy in mouse heart

Abstract

The L-type Ca2+ current (ICa,L) plays an important role in the regulation of cardiac contractility. However, there is little data with regard to the significance of the ICa,L-independent mechanism of β-adrenoceptor mediated positive inotropy. The effects of isoproterenol (ISO) on ICa,L and contractility in the presence of Ca2+ channel blockers (nifedipine, verapamil) were examined in adult mouse ventricular myocytes. ISO increased contractility over the level before the administration of Ca2+ channel blocker, although it had a very limited effect on ICa,L. The positive inotropy of ISO disappeared after administration of Ni2+, an inhibitor of the Na+-Ca2+ exchanger. The addition of ISO after nifedipine pretreatment also increased the [Ca2+]i transient over the control level and the application of Ni2+ or KB-R7943, a selective Na+-Ca2+ exchange inhibitor (reverse mode), abolished the increase in [Ca2+]i transient. Therefore, an ICa,L-independent mechanism plays a significant role in β-adrenoceptor mediated positive inotropy. The Na+-Ca2+ exchanger is necessary for the development of this action. Copyright © 2002 by the Japanese Heart Journal.