Ethanol effects on voltage-dependent membrane conductances: comparative sensitivity of channel populations inAplysia neurons

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Abstract
The study of ethanol (EtOH) action is interesting because of its clinical relevance and for the insights it provides into structure-function relationships of excitable membranes. This paper describes the concentration dependencies of various parameters of four currents inAplysia cells. I Ca is the most sensitive of the currents studied. There was a significant reduction ofI Ca at concentrations of 50 mM EtOH. At low concentrations, the reduction of amplitude was the primary effect of ethanol, with the kinetics and voltage dependency of activation not affected. I Na andI A were also affected, but at EtOH levels higher than those which alteredI Ca. The primary effect of EtOH onI Na was a reduction in its amplitude, although the time to peak current flow was increased by EtOH. The effects of EtOH onI A were cell specific and, for the purposes of this paper, we examined the giant metacerebral cell (MCC). In MCC, the primary effect of EtOH onI A was an increase in the time course of inactivation. The time to peakI A was also increased by high concentrations of EtOH, but its amplitude was unaffected even at high concentrations. The delayed rectifier current,I K, was the most EtOH resistant of the currents examined. High EtOH concentrations augmented the amplitude ofI K, although even at 600 mM concentrations, the percentage change was only 30%. Our results indicate that the calcium channel is very susceptible to the influence of ethanol and is a serious candidate to be the primary target of EtOH action in the nervous system. The differential sensitivity of voltage-dependent currents and individual components of a given current suggests further experiments to probe the relationship between membrane structure and channel function in excitable membranes.