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

研究了全麻对培养的牛肾上腺髓细胞中几种不同类型离子通道的影响。在这些细胞中，我们之前的研究表明，碳甾醇通过烟碱受体-离子通道复合物诱导的钠内流或缬草碱通过电压依赖性钠通道诱导的钠内流导致钙通过电压依赖性钙通道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流入。苯环利定可抑制卡巴卡醇（IC_<50> 7.0 muM）或藜曲碱（IC_<50> 60.0 muM）引起的^<22>Na、^<45>Ca的内流和儿茶酚胺的分泌。氯胺酮的临床浓度抑制了碳甾醇诱导的事件（IC_<50> 40.0 muM），而抑制缬草碱诱导的事件（IC_<50> 260 muM）的作用较小。2.曲哌啶醇对左旋碱诱导的事件（IC_<50> ~ 34 muM）有抑制作用，而对卡波卡醇诱导的事件（IC_<50> ~ 100 muM）影响较小。苯环利定、氯胺酮和氟哌啶醇没有改变细胞外钾诱导的高浓度钙内流和儿茶酚胺分泌。[^3H]-苯环利定特异性结合的Scatchard分析显示两个不同的平衡解离常数（4.3和77.4 muM）。[^3H]甲萘醇、毒蕈碱、d-管柯碱、六甲铵、河豚毒素、蛇毒碱和蝎毒均不抑制-苯环利定的结合。氟哌啶醇（100 muM）和氯胺酮（100 muM）使[^3H]-苯环利定的结合率分别降至40.3和80.1%。这些结果表明，使用的全身麻醉剂结合两种不同类型的位点，每一种位点都与尼古丁受体-离子通道复合物和电压依赖性钠通道在功能上相关，并抑制钠内流。麻醉剂不干扰电压依赖性钙通道，但抑制钠内流导致钙内流和儿茶酚碱引起的儿茶酚胺分泌减少。

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.