Details

Autor(en) / Beteiligte

• Wang, Y. G
• Zima, A. V
• Ji, X
• Pabbidi, R
• Blatter, L. A
• Lipsius, S. L

Titel

Ginsenoside Re suppresses electromechanical alternans in cat and human cardiomyocytes

Ist Teil von

• American journal of physiology. Heart and circulatory physiology, 2008-08, Vol.295 (2), p.H851-H859

Ort / Verlag

United States: American Physiological Society

Erscheinungsjahr

2008

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 Ca 2+ 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 Ca 2+ concentration ([Ca 2+ ] i ) transient alternans. Re exerted no significant effects on baseline action potential configuration or sarcolemmal L-type Ca 2+ 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 [Ca 2+ ] i transient amplitude and decreased sarcoplasmic reticulum (SR) Ca 2+ content, resulting in an increase in fractional SR Ca 2+ release. In SR microsomes isolated from cat ventricles, Re had no effect on SR Ca 2+ uptake. Re increased the open probability of ryanodine receptors (RyRs), i.e., SR Ca 2+ -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 Ca 2+ release underlying EMA. electrophysiology; Ca 2+ transients; arrhythmias Address for reprint requests and other correspondence: S. Lipsius, Dept. of Physiology, Loyola Univ. Medical Center, 2160 S. First Ave., Maywood, IL 60153 (e-mail: slipsiu{at}lumc.edu )