Action of anesthetics on acetylcholine receptor and voltage-dependent Na channel in cultured adrenal medullary cells.

在培养的牛肾上腺髓质细胞中研究了全身麻醉药对几种不同类型离子通道的影响。在这些细胞中，我们以前的研究表明，卡巴胆碱通过烟碱受体-离子通道复合物诱导的钠内流或藜芦碱通过电压依赖性钠通道诱导的钠内流引起电压依赖性钙通道的钙内流并触发儿茶酚胺分泌，而高浓度的细胞外钾直接激活电压依赖性钙通道而不增加钠内流.苯环利定抑制<22><45>卡巴胆碱（IC_<50>7.0 μ M）或藜芦啶（IC_ 60.0 μ M）<50>引起的~（13）Na、~（13）Ca内流和儿茶酚胺分泌。临床浓度的氯胺酮抑制卡巴胆碱诱导的事件（IC_<50>40.0 μ M），而较少抑制藜芦碱诱导的事件（IC_<50>260 μ M）。氟哌利多抑制藜芦碱诱导的事件（IC_<50>34 μ M），但对卡巴胆碱诱导的事件影响较小（IC_<50>&gt;100 μ M）.苯环己哌啶、氯胺酮和氟哌利多对高浓度钾诱导的细胞外<45>钙内流和儿茶酚胺分泌无明显影响.对[^3H]-苯环利定特异性结合的Scatchard分析揭示了两个不同的平衡解离常数（4.3和77.4 μ M）。卡巴胆碱、毒蝇碱、d-筒箭毒碱、六甲双铵、河豚毒素、野百合碱和蝎毒不抑制[^3H]-苯环利定结合。氟哌利多（100 μ M）和氯胺酮（100 μ M）使[^3H]-苯环利定的结合率分别降低到对照组的40.3%和80.1%。4.这些结果表明，所用的全身麻醉药与两类不同的位点结合，每一类位点在功能上都与烟碱受体-离子通道复合物和电压依赖性Na通道相关，并抑制Na内流。麻醉剂不干扰电压依赖性Ca通道，但抑制Na内流导致卡巴胆碱和藜芦啶引起的Ca内流和儿茶酚胺分泌减少。

The effects of general anesthetics on several distinct types of ion channels were investigated in cultured bovine adrenal medullary cells. In these cells, our previous studies suggest that carbachol-induced Na influx via nicotinic receptor-ion channel complex or veratridine-induced na influx via voltage-dependent Na channel causes ca influx via voltage-dependeut Ca channel and triggers catecholamine secretion, whereas high concentration of extracellular potassium directly activates voltage-dependent Ca channel without increasing Na influx.1. Phencyclidine inhibited influx of ^<22>Na, ^<45>Ca and secretion of catecholamines caused by carbachol (IC_<50> 7.0 muM) or by veratridine (IC_<50> 60.0 muM). Clinical concentrations of ketamine suppressed carbachol-induced events (IC_<50> 40.0 muM) with less inhibiting veratridine-induced events (IC_<50> 260 muM). droperidol suppressed veratridine-induced events (IC_<50> 34 muM), but less affected carbachol-induced events (IC_<50> >100 muM).2. Phencyclidine, ketamine and droperidol did not alter high concentration of extracellular potassium-induced ^<45>Ca influx and catecholamine secretion.3. Scatchard analysis of [^3H]-phencyclidine specific binding revealed two different equilibrium dissociation constants (4.3 and 77.4 muM). [^3H]-Phencyclidine binding was not inhibited by carbachol, muscarine, d-tubocurarine, hexamethonium, tetrodotoxin, veratridine and -scorpion venom. Droperidol (100 muM) and ketamine (100 muM) reduced [^3H]-phencyclidine binding to 40.3 and 80.1% of control.4.These results indicate that general anesthetics used bind to two distinct classes of sites, each of which is functionally associated with nicotinic receptor-ion channel complex and with voltage-dependent Na channel and inhibit Na influx. Anesthetics do not interfere with voltage-dependent Ca channel, but inhibition of Na influx leads to the reduction of Ca influx and catecholamine secretion caused by carbachol and by veratridine.