钾通道开放剂SR 44866对兔、豚鼠和人心肌纤维动作电位的影响。
Effects of SR 44866, a potassium channel opener, on action potentials of rabbit, guinea pig, and human heart fibers.
作者信息
Gautier P, Bertrand J P, Guiraudou P
机构信息
Sanofi Recherche, Montpellier, France.
出版信息
J Cardiovasc Pharmacol. 1991 May;17(5):692-700. doi: 10.1097/00005344-199105000-00002.
The effects of various concentrations (3 x 10(-8) - 1 x 10(-5) M) of SR 44866, a K+ channel opener, on action potential (AP) characteristics were investigated in isolated rabbit sinoatrial node (SAN), rabbit Purkinje fibers, guinea pig ventricle, human atrium, and human papillary muscle. SR 44866 (up to 1 x 10(-5) M), like cromakalim and pinacidil, did not modify SAN AP and automaticity of the rabbit heart. In atrial, Purkinje and ventricular fibers of animal and human hearts, SR 44866 did not significantly change membrane resting potential, AP amplitude, or maximum rate of phase 0 (dV/dtmax). The main AP modifications induced by SR 44866 were concentration-dependent reductions in plateau amplitude and AP duration (APD): IC50 2 x 10(-7), 7 x 10(-7), 1.4 x 10(-6), 2.5 x 10(-6), and much greater than 10(-5) M for human atrium, human ventricle, guinea pig ventricle, rabbit Purkinje, and rabbit atrium, respectively. In isolated guinea pig heart, SR 44866 induced decreases in contractions (IC50 1.7 x 10(-6) M) and coronary perfusion pressure (CPP) (IC50 2.1 x 10(-8) M) with a very slight reduction (5% at 1 x 10(-6) M) in spontaneous heart rate (HR). Negative inotropic effect (guinea pig) and APD shortenings (guinea pigs and humans) of SR 44866 (1 x 10(-6) and 3.10(-6) M) were antagonized by glibenclamide (3 x 10(-7) to 3 x 10(-6) M), a specific blocker of cardiac K+ATP channels. The data support the hypothesis that SR 44866 activates ATP-sensitive K+ channels, which are present in the atria and ventricles of the human heart but not in pacemaker cells of rabbit SAN.
研究了钾通道开放剂SR 44866的不同浓度（3×10⁻⁸ - 1×10⁻⁵ M）对离体兔窦房结（SAN）、兔浦肯野纤维、豚鼠心室、人心房和人乳头肌动作电位（AP）特性的影响。SR 44866（高达1×10⁻⁵ M）与克罗卡林和平卡地尔一样，不改变兔心脏的窦房结动作电位和自律性。在动物和人的心房、浦肯野纤维和心室纤维中，SR 44866不会显著改变膜静息电位、动作电位幅度或0期最大速率（dV/dtmax）。SR 44866诱导的主要动作电位改变是平台期幅度和动作电位时程（APD）的浓度依赖性降低：人心房、人心室、豚鼠心室、兔浦肯野纤维和兔心房的IC50分别为2×10⁻⁷、7×10⁻⁷、1.4×10⁻⁶、2.5×10⁻⁶和远大于10⁻⁵ M。在离体豚鼠心脏中，SR 44866诱导收缩力降低（IC50 1.7×10⁻⁶ M）和冠状动脉灌注压（CPP）降低（IC50 2.1×10⁻⁸ M），自发心率（HR）仅有非常轻微的降低（1×10⁻⁶ M时为5%）。格列本脲（3×10⁻⁷至3×10⁻⁶ M）可拮抗SR 44866（1×10⁻⁶和3×10⁻⁶ M）的负性肌力作用（豚鼠）和动作电位时程缩短作用（豚鼠和人），格列本脲是心脏K⁺ATP通道的特异性阻滞剂。这些数据支持以下假说：SR 44866激活ATP敏感性钾通道，该通道存在于人心房和心室中，但不存在于兔窦房结的起搏细胞中。
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