Na+-induced Ca2+ influx through reverse mode of Na+-Ca2+ exchanger in mouse ventricular cardiomyocyte.

Autor:	Yan ZY; Department of Pharmacology, Harbin Medical University, Harbin, China.; Riley Heart Research Center, Division of Pediatric Cardiology, Herman B. Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, USA., Ban T; Department of Pharmacology, Harbin Medical University, Harbin, China.; Key Laboratory of Cardiovascular Medicine Research, Harbin Medical University, Harbin, China., Fan Y; Department of Pharmacology, Harbin Medical University, Harbin, China., Chen WR; Department of Pharmacology, Harbin Medical University, Harbin, China., Sun HL; Department of Pharmacology, Da-Qing Campus of Harbin Medical University, Da-Qing, China., Chen H; Department of Pharmacology, Da-Qing Campus of Harbin Medical University, Da-Qing, China., Qiao QF; Department of Pharmacology, Harbin Medical University, Harbin, China.; Key Laboratory of Cardiovascular Medicine Research, Harbin Medical University, Harbin, China., Li BY; Department of Pharmacology, Harbin Medical University, Harbin, China.
Jazyk:	angličtina
Zdroj:	Oncotarget [Oncotarget] 2015 Sep 15; Vol. 6 (27), pp. 23272-80.
DOI:	10.18632/oncotarget.4878
Abstrakt:	Background: Dobutamine is commonly used for clinical management of heart failure and its pharmacological effects have long been investigated as inotropics via β-receptor activation. However, there is no electrophysiological evidence if dobutamine contributes inotropic action due at least partially to the reverse mode of Na+-Ca2+ exchanger (NCX) activation. Methods: Action potential (AP), voltage-gated Na+ (INa), Ca2+ (ICa), and K+ (Ito and IK1) currents were observed using whole-cell patch technique before and after dobutamine in ventricular cardiomyocytes isolated from adult mouse hearts. Another sets of observation were also performed with Kb-r7943 or in the solution without [Ca2+]o. Results: Dobutamine (0.1-1.0 μM) significantly enhanced the AP depolarization with prolongation of AP duration (APD) in a concentration-dependent fashion. The density of INa was also increased concentration-dependently without alternation of voltage-dependent steady-status of activation and inactivation, reactivation as well. Whereas, the activities for ICa, Ito, and IK1 were not changed by dobutamine. Intriguingly, the dobutamine-mediated changes in AP repolarization were abolished by 3 μM Kb-r7943 pretreatment or by simply removing [Ca2+]o without affecting accelerated depolarization. Additionally, the ratio of APD50/APD90 was not significantly altered in the presence of dobutamine, implying that effective refractory period was remain unchanged. Conclusions: This novel finding provides evidence that dobutamine upregulates of voltage-gated Na+ channel function and Na+ influx-induced activation of the reverse mode of NCX, suggesting that dobutamine may not only accelerate ventricular contraction via fast depolarization but also cause Ca2+ influx, which contributes its positive inotropic effect synergistically with β-receptor activation without increasing the arrhythmogenetic risk.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu