Shirasaka Tetsuro, Yoshimura Yasuhiro, Qiu De-Lai, Takasaki Mayumi
Departments of *Anesthesiology and †Physiology, Miyazaki Medical College, Kiyotake, Japan.
Anesth Analg. 2004 Apr;98(4):1017-1023. doi: 10.1213/01.ANE.0000107960.89818.35.
The mechanism of hypotension induced by anesthetics is not completely understood. Because no electrophysiologic examination of the effects of propofol on the central nervous system has shown its involvement in the control of sympathetic and cardiovascular functions, we investigated the actions of propofol on rat hypothalamic paraventricular nucleus (PVN) neurons using the whole-cell mode of the patch-clamp technique in rat hypothalamic PVN slice preparations. Propofol induced Cl(-) currents at concentrations of 10(-5) and 10(-4) M, which were sensitive to picrotoxin and, to a lesser extent, to strychnine. Propofol (10(-6) M) enhanced gamma-aminobutyric acid(A) (GABA(A); 10(-6) M)-induced current synergistically. Moreover, propofol (10(-5) and 10(-4) M) significantly increased the decay time of evoked-inhibitory postsynaptic currents, which suggests a postsynaptic modulation of GABA(A) receptors. In addition, propofol (10(-5), 10(-4), and 2 x 10(-4) M) reversibly inhibited voltage-gated Ca(2+) currents. Taken together, these results suggest that propofol enhancement of GABA(A)-receptor mediated currents and inhibition of voltage-gated Ca(2+) currents at the central level, which is involved in the control of cardiovascular and sympathetic functions may be, at least in part, involved in general anesthetic-induced cardiovascular and sympathetic depression.
We investigated the actions of propofol on the rat hypothalamic paraventricular nucleus neurons, which are involved in the control of cardiovascular and sympathetic functions. The results suggest that propofol enhancement of gamma-aminobutyric acid(A)-receptor mediated currents and inhibition of voltage-gated Ca(2+) currents at the central level may be, at least in part, involved in general anesthetic-induced cardiovascular and sympathetic depression.
麻醉剂引起低血压的机制尚未完全明确。由于尚无关于丙泊酚对中枢神经系统作用的电生理检查显示其参与交感神经和心血管功能的控制，因此我们采用膜片钳技术的全细胞模式，在大鼠下丘脑室旁核（PVN）脑片制备中研究了丙泊酚对大鼠下丘脑室旁核神经元的作用。丙泊酚在10⁻⁵和10⁻⁴ M浓度时可诱导Cl⁻电流，该电流对苦味毒敏感，对士的宁的敏感性稍低。丙泊酚（10⁻⁶ M）可协同增强γ-氨基丁酸A（GABA(A)；10⁻⁶ M）诱导的电流。此外，丙泊酚（10⁻⁵和10⁻⁴ M）显著增加诱发抑制性突触后电流的衰减时间，这表明对GABA(A)受体存在突触后调制。另外，丙泊酚（10⁻⁵、10⁻⁴和2×10⁻⁴ M）可逆性抑制电压门控Ca²⁺电流。综上所述，这些结果表明丙泊酚增强GABA(A)受体介导的电流以及在中枢水平抑制电压门控Ca²⁺电流，而这与心血管和交感神经功能的控制有关，可能至少部分参与了全身麻醉引起的心血管和交感神经抑制。
我们研究了丙泊酚对参与心血管和交感神经功能控制的大鼠下丘脑室旁核神经元的作用。结果表明，丙泊酚增强γ-氨基丁酸A受体介导的电流以及在中枢水平抑制电压门控Ca²⁺电流可能至少部分参与了全身麻醉引起的心血管和交感神经抑制。
