- 作者: Wen-Pin Chen; Ming-Jai Su
- 作者服務機構: Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, Taiwan
- 中文摘要: --
- 英文摘要: The aim of this study was to determine the effect of pro-tein kinase C (PKC) activation on intracellular Ca2+ tran-sient and its relation to a1-adrenoceptor (a1-AR)-stimulat-ed negative inotropic response in rat ventricles. The elec-tromechanical responses to phenylephrine (PE) in ratventricular muscles were concomitantly examined usingthe conventional microelectrode method. The responsesof intracellular Ca2+ transient and cell contractions to PEin the absence of certain pharmacological interventionswere ascertained in fura-2-loaded myocytes. The in-fluence of PE on L-type Ca2+ current (ICa,L)was also exam-ined using a voltage clamp in a whole-cell configuration.PE did not alter the action potential parameters duringthe negative inotropic phase.The negative inotropiceffect (ME) was inhibited by prazosin, chloroethylclonid-ine (CEC) and staurosporine, but was insensitive to per-tussis toxin. Desensitization of PKC after prolonged pre-treatment of rat ventricles with PDBu also abolished theNIE of PE. Caffeine modulated the NIE, but thapsigargindid not. The evoked intracellular Ca2+ transient and cellcontraction were initially decreased by PE, while ICa,L wasnot altered. Prazosin and staurosporine significantly in-hibited the responses. Our data indicated that a1AR-mediated NIE in rat ventricular muscles was due to thedecrease of intracellular Ca2+ transients by the modula-tion of PKC on Ca2+-releasing channels signaling througha CEC-sensitive a1AR subtype.
- 中文關鍵字: --
- 英文關鍵字: --