Hirota K, Ito Y, Momose Y, Kuze S
Department of Anesthesiology, Faculty of Medicine, Toyama Medical and Pharmaceutical University.
Masui. 1990 Nov;39(11):1460-6.
In order to assess directly the actions of halothane on myocardium, especially on the Ca2+ channel we studied effects of halothane on electrophysiological and biochemical properties in single ventricular myocytes isolated enzymatically from guinea pig hearts. Membrane potentials and the slow inward Ca2+ current (ICa) were recorded with a suction microelectrode technique and a whole cell voltage clamp technique. The plateau duration of the action potential, maintained by ICa, and ICa was depressed by 2% halothane (to 58% and 29% of control respectively). To define the site on which halothane acts in the cell membrane, we measured cyclic adenosine monophosphate (cAMP) content of single ventricular myocytes using radioimmunoassay. One percent (1%) and 2% halothane directly produced a dose-dependent decrease in myocardial cAMP content (79% and 65% of control respectively). In conclusion, the present results suggest that the decrease of ICa by halothane participates in the observed depression of the action potential plateau phase and demonstrate that halothane depression of ICa is in part due to an inactivation of phosphorylation dependent gate in the Ca2+ channel resulting from the decrease in cAMP content by halothane.
为了直接评估氟烷对心肌，尤其是对Ca2+通道的作用，我们研究了氟烷对从豚鼠心脏酶解分离的单个心室肌细胞电生理和生化特性的影响。采用吸引微电极技术和全细胞电压钳技术记录膜电位和缓慢内向Ca2+电流（ICa）。由ICa维持的动作电位平台期和ICa被2%氟烷抑制（分别降至对照的58%和29%）。为了确定氟烷在细胞膜上的作用位点，我们使用放射免疫分析法测量单个心室肌细胞的环磷酸腺苷（cAMP）含量。1%和2%的氟烷直接导致心肌cAMP含量呈剂量依赖性降低（分别为对照的79%和65%）。总之，目前的结果表明，氟烷导致的ICa降低参与了所观察到的动作电位平台期的抑制，并表明氟烷对ICa的抑制部分是由于氟烷使cAMP含量降低，导致Ca2+通道中磷酸化依赖性门失活。
