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

Zhen Yu Yan, Tao Ban, Yao Fan, Wei Ran Chen, Hong Li Sun, Hanying Chen, Quo Fen Qiao, Bai Yan Li

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)23272-23280
Number of pages9
JournalOncotarget
Volume6
Issue number27
DOIs
StatePublished - 2015

Keywords

  • Action potential
  • Dobutamine
  • Pathology Section
  • Reverse mode of Na-Ca+ exchanger
  • Ventricular cardiomyocyte
  • Voltage-gated ion channel

ASJC Scopus subject areas

  • Oncology

Fingerprint Dive into the research topics of 'Na<sup>+</sup>-induced Ca<sup>2+</sup>+ influx through reverse mode of Na<sup>+</sup>-Ca<sup>2+</sup>+ exchanger in mouse ventricular cardiomyocyte'. Together they form a unique fingerprint.

Cite this