Document Detail

Inhibition of L-type Ca(2+) current in Guinea pig ventricular myocytes by cisapride.
MedLine Citation:
PMID:  15067213     Owner:  NLM     Status:  MEDLINE    
The effect of cisapride on L-type Ca(2+) current (I(Ca,L)) was studied in guinea pig ventricular myocytes using a whole-cell voltage-clamp technique and a conventional action potential recording method. Myocytes were held at -40 mV, and internally dialyzed and externally perfused with Na(+)- and K(+)-free solutions; cisapride elicited a concentration-dependent block of peak I(Ca,L), with a half-maximum inhibition concentration (IC(50)) of 46.9 microM. There was no shift in the reversal potential, nor any change in the shape of the current-voltage relationship of I(Ca,L) in the presence of cisapride. Inhibition of cisapride was not associated with its binding to serotonin or to alpha-adrenergic receptors because ketanserin, SB203186, and prazosin had no effect on the inhibitory action of cisapride on I(Ca,L). Cisapride elicited a tonic block and a use-dependent block of I(Ca,L). These blocking effects were voltage dependent as the degree of inhibition at -40 mV was greater than that at -70 mV. Cisapride shifted the steady-state inactivation curve of I(Ca,L) in the negative direction, but had no effect on the steady-state activation curve. Cisapride also delayed the kinetics of recovery of I(Ca,L) from inactivation. At a slow stimulation frequency (0.1 Hz), the action potential duration in guinea pig papillary muscles showed biphasic effects; it was prolonged by lower concentrations of cisapride, but shortened by higher concentrations. These findings suggest that cisapride preferentially binds to the inactivated state of L-type Ca(2+) channels. The inhibitory effect of cisapride on I(Ca,L) might play an important role in its cardiotoxicity under pathophysiological conditions, such as myocardial ischemia.
Chern-En Chiang; Tsui-Min Wang; Hsiang-Ning Luk
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of biomedical science     Volume:  11     ISSN:  1021-7770     ISO Abbreviation:  J. Biomed. Sci.     Publication Date:    2004 May-Jun
Date Detail:
Created Date:  2004-04-06     Completed Date:  2004-12-06     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  9421567     Medline TA:  J Biomed Sci     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  303-14     Citation Subset:  IM    
Copyright Information:
Copyright 2004 National Science Council, ROC and S. Karger AG, Basel
Division of Cardiology, Taipei Veterans General Hospital and National Yang-Ming University, Taipei, Taiwan, ROC.
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MeSH Terms
Action Potentials
Calcium Channels, L-Type / drug effects*,  physiology
Cisapride / pharmacology*
Guinea Pigs
Heart Ventricles / drug effects*
Ventricular Function
Reg. No./Substance:
0/Calcium Channels, L-Type; 81098-60-4/Cisapride

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