硫喷妥钠、氯胺酮和丙泊酚对猪气管平滑肌细胞电压依赖性Ca2+通道的抑制作用。

Inhibitory effects of thiopental, ketamine, and propofol on voltage-dependent Ca2+ channels in porcine tracheal smooth muscle cells.

作者信息

Yamakage M, Hirshman C A, Croxton T L

机构信息

Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Medical Institutions, School of Hygiene and Public Health, Baltimore, Maryland, USA.

出版信息

Anesthesiology. 1995 Dec;83(6):1274-82. doi: 10.1097/00000542-199512000-00018.

DOI:10.1097/00000542-199512000-00018

PMID:8533920

Abstract

BACKGROUND

Intravenously administered anesthetics directly inhibit airway smooth muscle contraction. Because many anesthetic agents affect membrane ion channel function and sustained contraction of airway smooth muscle requires the influx of Ca2+ through voltage-dependent Ca2+ channels, it was hypothesized that intravenous anesthetics inhibit airway smooth muscle voltage-dependent Ca2+ channels.

METHODS

Porcine tracheal smooth muscle cells were enzymatically dispersed and studied using whole-cell, patch-clamp techniques. The cells were exposed to thiopental (10(-7)-3 x 10(-4) M), ketamine (10(-6)-10(-3) M), or propofol (10(-7)-3 x 10(-4) M) while recording macroscopic voltage-activated Ca2+ currents (ICa).

RESULTS

Each intravenous anesthetic tested significantly inhibited ICa in a dose-dependent manner with 3 x 10(-4) M thiopental, 10(-3) M ketamine, and 3 x 10(-4) M propofol each causing approximately 50% depression of peak ICa, but with no apparent shift in the voltage dependence of induced ICa. After pretreatment with the Ca2+ channel agonist Bay K 8644, thiopental, but not ketamine or propofol, shifted the maximum ICa to more positive potentials. All three anesthetics promoted the inactivated state of the channel at more negative potentials, but propofol was less effective than thiopental or ketamine in this regard.

CONCLUSIONS

Three intravenous anesthetics evaluated in this study decreased the ICa of porcine tracheal smooth muscle cells but with subtle electrophysiologic differences. Hence, thiopental, ketamine, and propofol each inhibit L-type voltage-dependent Ca2+ channels of porcine tracheal smooth muscle cells but the molecular mechanisms involved may be agent specific. This inhibition may contribute to the airway smooth muscle relaxant effects of these agents observed in vitro at concentrations greater than those encountered clinically.

摘要

背景

静脉注射麻醉药可直接抑制气道平滑肌收缩。由于许多麻醉药会影响膜离子通道功能，且气道平滑肌的持续收缩需要钙离子通过电压依赖性钙离子通道内流，因此推测静脉麻醉药可抑制气道平滑肌电压依赖性钙离子通道。

方法

采用酶解法分离猪气管平滑肌细胞，并运用全细胞膜片钳技术进行研究。在记录宏观电压激活的钙离子电流（ICa）时，使细胞暴露于硫喷妥钠（10⁻⁷ - 3×10⁻⁴ M）、氯胺酮（10⁻⁶ - 10⁻³ M）或丙泊酚（10⁻⁷ - 3×10⁻⁴ M）中。

结果

每种受试静脉麻醉药均以剂量依赖性方式显著抑制ICa，3×10⁻⁴ M硫喷妥钠、10⁻³ M氯胺酮和3×10⁻⁴ M丙泊酚均可使峰值ICa降低约50%，但诱导ICa的电压依赖性无明显偏移。用钙离子通道激动剂Bay K 8644预处理后，硫喷妥钠可使最大ICa向更正电位偏移，而氯胺酮和丙泊酚则无此作用。所有三种麻醉药均可使通道在更负电位时促进失活状态，但在这方面丙泊酚的作用不如硫喷妥钠或氯胺酮有效。