title: The Na+-Ca2+ exchanger contributes to beta-adrenoceptor mediated positive inotropy in mouse heart.
abstract: The L-type Ca2+ current (I(Ca,L)) plays an important role in the regulation of cardiac contractility. However, there is little data with regard to the significance of the I(Ca,L)-independent mechanism of beta-adrenoceptor mediated positive inotropy. The effects of isoproterenol (ISO) on I(Ca,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 I(Ca,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 I(Ca,L)-independent mechanism plays a significant role in beta-adrenoceptor mediated positive inotropy. The Na+-Ca2+ exchanger is necessary for the development of this action.
authors.affiliation: First Department of Internal Medicine, Yamagata University School of Medicine, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Kubota
authors.forename: Hitonobu
authors.initials: H
authors.lastname: Tomoike
authors.forename: Xinquiang
authors.initials: X
authors.lastname: Han
authors.forename: Kiyoharu
authors.initials: K
authors.lastname: Sakurai
authors.forename: Masao
authors.initials: M
authors.lastname: Endoh
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D007545:Isoproterenol / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology; D009543:Nifedipine / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D019831:Sodium-Calcium Exchanger / Q000502:physiology*; D013268:Stimulation, Chemical; D014700:Verapamil / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D002316:Cardiotonic Agents; D011943:Receptors, Adrenergic, beta; D019831:Sodium-Calcium Exchanger; D014700:Verapamil; D009543:Nifedipine; D007545:Isoproterenol