The actions of some general anaesthetics on the potassium current of the squid giant axon.

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Abstract
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 and 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. 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 maximum sodium conductance, .hivin.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 methylflurane solutions, the voltage-clamped potassium currents exhibited pronounced inactivation-like behavior. These currents can be fitted by the Hodgkin-Huxley formalism if an inactivation term analogous to the sodium current inactivation is added. Most of the other anaesthetics studied also produced some inactivation (or droop) in the potassium currents. The effects of the various anaesthetics on the parameters of the Hodgkin-Huxley equations are consistent with the ideat that, in the squid giant axon, the reduction of potassium currents, like the reduction of sodium currents, originates from more than one type of interaction. The comparison of the two current systems suggests also that, as well as interacting with the adjacent lipid, certain anaesthetics may have an additional site of action in or on a membrane channel itself.

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