Ethanol reduces excitability in a subgroup of primary sensory neurons by activation of BKCa channels

Ethanol effects on the central nervous system have been well investigated a nd described in recent years; modulations, by ethanol, of several ligand-ga ted and voltage-gated ion channels have been found. In this paper, we descr ibe a shortening of action potential duration (APD) by ethanol in approxima te to 40% of small diameter neurons in rat dorsal root ganglia (DRG). In th ese neurons, designated as group A neurons, we observed an ethanol-induced increase in whole-cell outward-current. As iberiotoxin, a specific blocker of large-conductance calcium-activated K+ channels (BKCa channels), blocks the effects of ethanol, we investigated the interaction between these chann els and ethanol in outside-out patches. Open probability of BKCa channels w as increased 2-6 x depending on the concentration (40-80 mM approximate to 2-4 parts per thousand v/v) of ethanol. Functional consequences were a prol ongation of the refractory period, which was reversible after addition of i beriotoxin, and reduced firing frequency during ethanol application. In con trast, another type of neuron (group B) showed a prolonged APD during appli cation of ethanol which was irreversible in most cases. In 90% of cases, ne urons of group A showed a positive staining for isolectin B4 (I-B4), a mark er for nociceptive neurons. We suggest that the activation of BKCa channels induced by clinically relevant concentrations of ethanol, the resulting mo dulations of APD and refractory period of DRG neurons, might contribute to clinically well-known ethanol-induced analgesia and paresthesia.