The actions of some general anaesthetics on the potassium current of the squid giant axon.
The actions of some general anaesthetics on the potassium current of the squid giant axon.
复制标题
一些全身麻醉剂对鱿鱼巨轴突钾电流的作用。
DOI：
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发表时间：
1986
期刊：
影响因子：
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通讯作者：
B. Urban
中科院分区：
文献类型：
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作者：
D. Haydon;B. Urban
一些具有全身麻醉作用的有机小分子对乌贼巨大轴突电压依赖性钾电流的影响已经被研究。它们包括在先前的钠电流研究中检测到的三种麻醉药的代表（Haydon & Urban, 1983a, b, c），即非极性分子正戊烷，环戊烷和CCl4，几种正烷醇和吸入麻醉剂氯仿，氟烷，乙醚和甲氧基氟醚。在接触试验物质之前、期间和之后，分别记录完整轴突和细胞内灌注的轴突在电压钳下的钾电流，并用类似于Hodgkin & Huxley（1952）提出的方程拟合记录。稳态激活对膜电位的变化曲线和钾电导在60或70 mV膜电位下的降低曲线已被制成表格。在同一完整的轴突上，除甲氧基氟醚外，所有麻醉药对钾电流的减少都小于钠电流，减少幅度约为两倍或更多。对于正烷醇，丁醇到癸醇，确定了在60 mV膜电位下将钾电流降低50%所需的浓度。从正丁醇到正庚醇，每CH2吸附到作用位点的标准自由能估计为‐2.91 kJ mol‐1，而降低钠电流的标准自由能为‐3.04 kJ mol‐1。链长越长，烷烃的自由能越小。在麻醉浓度使钠电流降低50%的情况下，疏水物质正戊烷和环戊烷使最大钠电导gNa和70 mV时的钾电导gK70同样降低了约三分之一，而正烷醇对这两个参数的降低都不到10%。相比之下，乙醚和甲氧基氟醚对降低最大钾电导更有效。除正戊烷和正己烷外，所有测试物质都改变了钾稳态激活在去极化方向上的电压依赖关系。在钠电流和钾电流激活曲线的变化之间发现了广泛的定性相关性，但在定量上，两种变化之间的一致性很差。在正癸醇和甲氧基氟醚溶液中，电压箝位的钾电流表现出明显的失活行为。如果加入一个类似于钠电流失活的失活项，这些电流可以用霍奇金-赫胥黎形式拟合。（摘要删节为400字）
A number of small organic molecules with general anaesthetic action have been examined for their effects on the voltage‐dependent potassium current of the squid giant axon. They include representatives of the three classes of anaesthetics examined in previous studies on the sodium current (Haydon & Urban, 1983a, b, c), i.e. the non‐polar molecules n‐pentane, cyclopentane and CCl4, several n‐alkanols and the inhalation anaesthetics chloroform, halothane, diethyl ether and methoxyflurane. Potassium currents under voltage clamp were recorded in intact and in intracellularly perfused axons before, during and after exposure to the test substances, and the records were fitted with equations similar to those proposed by Hodgkin & Huxley (1952). Shifts in the curves of the steady‐state activation against membrane potential and reductions in the potassium conductance at 60 or 70 mV membrane potential have been tabulated. On the same intact axons, all the anaesthetics with the exception of methoxyflurane reduced potassium currents less than sodium currents by about a factor of two or more. For the n‐alkanols, butanol to decanol, the concentrations required to reduce the potassium current at 60 mV membrane potential by 50% were determined. For n‐butanol to n‐heptanol, the standard free energy per CH2 for adsorption to the site of action was estimated to be ‐2.91 kJ mol‐1 as compared with ‐3.04 kJ mol‐1 for reduction of the sodium current. The magnitude of the free energy decreased for alkanols with longer chain lengths. At anaesthetic concentrations that reduce the sodium current by 50%, the hydrophobic substances n‐pentane and cyclopentane reduced the maximal sodium conductance, gNa, and the potassium conductance at 70 mV, gK70, equally by about a third, while the n‐alkanols reduced both parameters by less than 10%. By contrast, diethyl ether and methoxyflurane were more effective in reducing the maximal potassium conductance. All of the test substances examined, except n‐pentane and n‐hexane, shifted the voltage dependence of the potassium steady‐state activation in the depolarizing direction. A broad qualitative correlation was found between the shifts in the activation curves for sodium and potassium currents but, quantitatively, the agreement between the two shifts was poor. In n‐decanol and methoxyflurane solutions, the voltage‐clamped potassium currents exhibited pronounced inactivation‐like behaviour. These currents can be fitted by the Hodgkin‐Huxley formalism if an inactivation term analogous to the sodium current inactivation is added.(ABSTRACT TRUNCATED AT 400 WORDS)