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This Article Full Text Full Text (PDF) All Versions of this Article: 295/2/H851    most recent 01242.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Wang, Y. G. Articles by Lipsius, S. L. PubMed PubMed Citation Articles by Wang, Y. G. Articles by Lipsius, S. L.

Ginsenoside Re suppresses electromechanical alternans in cat and human cardiomyocytes

Departments of Physiology, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois

Submitted 25 October 2007 ; accepted in final form 27 May 2008

Ginseng botanicals are increasingly used as complementary or alternative medicines for a variety of cardiovascular diseases, yet little is known about their cellular actions in cardiac muscle. Electromechanical alternans (EMA) is a proarrhythmic cardiac abnormality that results from disturbances of intracellular Ca²⁺ homeostasis. This study sought to determine whether a purified ginsenoside extract of ginseng, Re, exerts effects to suppress EMA and to gain insight into its mechanism of action. Alternans was induced by electrically pacing cardiomyocytes at room temperature. Re (10 nM) reversibly suppressed EMA recorded from cat ventricular and atrial myocytes and Langendorff-perfused cat hearts. In cat ventricular myocytes, Re reversibly suppressed intracellular Ca²⁺ concentration ([Ca²⁺]_i) transient alternans. Re exerted no significant effects on baseline action potential configuration or sarcolemmal L-type Ca²⁺ current (I_Ca,L), Na⁺ current, or total K⁺ conductance. In human atrial myocytes, Re suppressed mechanical alternans and exerted no effect on I_Ca,L. In cat ventricular myocytes, Re increased [Ca²⁺]_i transient amplitude and decreased sarcoplasmic reticulum (SR) Ca²⁺ content, resulting in an increase in fractional SR Ca²⁺ release. In SR microsomes isolated from cat ventricles, Re had no effect on SR Ca²⁺ uptake. Re increased the open probability of ryanodine receptors (RyRs), i.e., SR Ca²⁺-release channels, isolated from cat ventricles and incorporated into planar lipid bilayers. We concluded that ginsenoside Re suppresses EMA in cat atrial and ventricular myocytes, cat ventricular muscle, and human atrial myocytes. The effects of Re are not mediated via actions on sarcolemmal ion channels or action potential configuration. Re acts via a subcellular mechanism to enhance the opening of RyRs and thereby overcome the impaired SR Ca²⁺ release underlying EMA.

electrophysiology; Ca²⁺ transients; arrhythmias