- 作者: Chern-En Chiang; Tsui-Min Wang; Hsiang-Ning Luk
- 作者服務機構: Division of Cardiology, Taipei Veterans General Hospital and National Yang-Ming University, Graduate Institute of Medical Science, Taipei Medical University, Department of Anesthesiology, Chang-Gung Memorial Hospital, Taipei, Taiwan(ROC)
- 中文摘要: --
- 英文摘要: The effect of cisapride on L-type Ca current (/ ) wasstudied in guinea pig ventricular myocytes using awhole-cell voltage-clamp technique and a conventionalaction potential recording method. Myocytes were heldat -40 mV, and internally dialyzed and externally per-fused with Na - and K -free solutions; cisapride elicited aconcentration-dependent block of peak / , with a half-maximum inhibition concentration (IC ) of 46.9 μM.There was no shift in the reversal potential, nor anychange in the shape of the current-voltage relationshipof / in the presence of cisapride. Inhibition of cisapridewas not associated with its binding to serotonin or to α-adrenergic receptors because ketanserin, S13203186, andprazosin had no effect on the inhibitory action of cisa-pride on / . Cisapride elicited a tonic block and a use-dependent block of / . These blocking effects were vol-tage dependent as the degree of inhibition at -40 mVwas greater than that at -70 mV. Cisapride shifted thesteady-state inactivation curve of / in the negativedirection, but had no effect on the steady-state activationcurve. Cisapride also delayed the kinetics of recovery of/ from inactivation. At a slow stimulation frequency(0.1 Hz), the action potential duration in guinea pig papil-lary muscles showed biphasic effects; it was prolongedby lower concentrations of cisapride, but shortened byhigher concentrations. These findings suggest that cisa-pride preferentially binds to the inactivated state of L-type Ca channels. The inhibitory effect of cisapride on/ might play an important role in its cardiotoxicityunder pathophysiological conditions, such as myocar-dial ischemia.
- 中文關鍵字: --
- 英文關鍵字: --