ReferenceID 3520

Polydatin modulates Ca(2+) handling, excitation-contraction coupling and β-adrenergic signaling in rat ventricular myocytes

J Mol Cell Cardiol

Polydatin (PD), a resveratrol glucoside, has recently been suggested to have cardioprotective effects against heart diseases, including ischemia-reperfusion injury and pressure-overload induced ventricular remodeling. Ho

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Reference Id
3520
Evidence Id
20110
Core Evidence Id
20110
Source Reference Id
344
Herb2 Reference Id
HBREF000634
Subject Paper Key
HBIN040403_22921781
Pubmed Id
22921781
Doi
10.1016/j.yjmcc.2012.08.009
Paper Title
Polydatin modulates Ca(2+) handling, excitation-contraction coupling and β-adrenergic signaling in rat ventricular myocytes
Paper Abstract
Polydatin (PD), a resveratrol glucoside, has recently been suggested to have cardioprotective effects against heart diseases, including ischemia-reperfusion injury and pressure-overload induced ventricular remodeling. However, the mechanisms are poorly understood. This study aims to investigate the direct effects of PD on cardiac Ca(2+) handling and excitation-contraction (EC) coupling to explore the potential role of which in PD-mediated cardioprotection. We found that micromolar PD decreased action potential-elicited Ca(2+) transient, but slightly increased cell shortening. The contradictory response could be attributed to PD increasing myofilament Ca(2+) sensitivity. Exploring the activities of the two types of Ca(2+) channels, L-type Ca(2+) channels (LCCs) and ryanodine receptors (RyRs), reveals that PD dose-dependently decreased LCC current (I(Ca)), but increased frequency of spontaneous Ca(2+) sparks, the elementary Ca(2+) releasing events reflecting RyR activity in intact cells. PD dose-dependently increased the gain of EC coupling. In contrast, PD dose-dependently decreased SR Ca(2+) content. Furthermore, PD remarkably negated β-adrenergic receptor (AR) stimulation-induced enhancement of I(Ca) and Ca(2+) transients, but did not inhibit β-AR-mediated inotropic effect. Inhibition of nitric oxide synthase (NOS) with L-NAME abolished PD regulation of I(Ca) and Ca(2+) spark rate, and significantly inhibited the alteration of Ca(2+) transient and myocyte contractility stimulated by PD. These results collectively indicate that PD modulated cardiac EC coupling mainly by inversely regulating LCC and RyR activity and increasing myofilament Ca(2+) sensitivity through increasing intracrine NO, resulting in suppression of Ca(2+) transient without compromising cardiac contractility. The unique regulation of PD on cardiac EC coupling and responsiveness to β-AR signaling implicates that PD has potential cardioprotective effects against Ca(2+) mishandling related heart diseases.
Journal
J Mol Cell Cardiol
Publish Year
2012
Experiment Subject
Experiment Type
Others
Phenotype Related
Heart Diseases
Paper Title Cn
Paper Title En
Polydatin modulates Ca(2+) handling, excitation-contraction coupling and β-adrenergic signaling in rat ventricular myocytes
Bilingual Status
semi_complete