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DM Lovinger and Q Zhou
Department of Molecular Physiology and Biophysics, Vanderbilt University Medical School, Nashville, Tennessee.
Trichloroethanol (TCEt) potentiated ion current mediated by 5- hydroxytryptamine (5-HT)3 receptors in isolated adult rat nodose ganglion neurons. The magnitude of potentiation of peak current amplitude increased with increasing TCEt concentrations from 0.5 to 5 mM. The rate of decay of current also increased as a function of TCEt concentration. Steady-state current was unaffected by TCEt at concentrations up to 10 mM. A high concentration of TCEt (25 mM) potentiated peak current but inhibited steady-state current. Potentiation appeared to involve an increase in agonist potency as the magnitude of potentiation of peak current decreased with increasing agonist concentration. Agonist application before TCEt treatment decreased the magnitude of potentiation elicited by 5 mM TCEt. These observations indicate that the potentiating action of TCEt arises from an increase in the efficacy with which 5-HT activates current. TCEt appears to facilitate transitions from closed to open states more readily than transitions from desensitized to open states. These observations are consistent with the hypothesis that 5-HT3 receptor function may contribute to the behavioral pharmacology of alcohols and related sedative/hypnotic agents.
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