DIFFERENTIAL SENSITIVITIES OF TTX-RESISTANT AND TTX-SENSITIVE SODIUM-CHANNELS TO ANESTHETIC CONCENTRATIONS OF ETHANOL IN RAT SENSORY NEURONS

Ethanol at concentration of 200 mM induces anesthesia in experimental animals and depresses neurotransmission in isolated spinal cords. To d etermine whether actions on primary afferent nerve terminals contribut e to ethanol's depressant effects on spinal cord, a study was undertak en to test whether ethanol blocks sodium currents (I-Na) in dorsal roo t ganglion neurons (DRGn). Whole-cell patch clamp was used to examine I-Na in DRGn isolated from 1- to 15-day-old rats. At a holding potenti al of -80 mV ethanol (200 mM) decreased peak tetrodotoxin-resistant (T TX-R) and tetrodotoxin-sensitive (TTX-S) I-Na by 19.0% +/- 2.7 (mean /- SEM) and 8.5% +/- 2.2, respectively. Maximal available I-Na was red uced to 82 +/- 4% (TTX-R) and 93 +/- 1% (TTX-S) of control. Steady-sta te inactivation curves were shifted in the hyperpolarizing direction b y 2.1 +/- 0.2 mV (TTX-R) and 1.1 +/- 0.1 mV (TTX-S). At prepulse poten tials of -30 mV (TTX-R) and -70 mV (TTX-S), these shifts contributed a n additional 17 +/- 1% (TTX-R) and 7 +/- 1% (TTX-S) reduction in avail able I-Na. Ethanol thus selectively induced both voltage-independent a nd voltage-dependent block of TTX-R I-Na in DRGn. Because DRGn TTX-R s odium channels are associated with small-diameter primary afferent fib ers, these results are consistent with a role for ethanol actions on s odium channels in depression of nociceptive-related neurotransmission in spinal cord. J. Neurosci. Res. 54:433-443, 1998. (C) 1998 Wiley-Lis s, Inc.