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 determine whether actions on primary afferent nerve terminals contribute to ethanol's depressant effects on spinal cord, a study was undertaken to test whether ethanol blocks sodium currents (I(Na)) in dorsal root 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 potential of -80 mV ethanol (200 mM) decreased peak tetrodotoxin-resistant (TTX-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 reduced to 82 +/- 4% (TTX-R) and 93 +/- 1% (TTX-S) of control. Steady-state inactivation curves were shifted in the hyperpolarizing direction by 2.1 +/- 0.2 mV (TTX-R) and 1.1 +/- 0.1 mV (TTX-S). At prepulse potentials of -30 mV (TTX-R) and -70 mV (TTX-S), these shifts contributed an additional 17 +/- 1% (TTX-R) and 7 +/- 1% (TTX-S) reduction in available I(Na). Ethanol thus selectively induced both voltage-independent and voltage-dependent block of TTX-R I(Na) in DRGn. Because DRGn TTX-R sodium channels are associated with small-diameter primary afferent fibers, these results are consistent with a role for ethanol actions on sodium channels in depression of nociceptive-related neurotransmission in spinal cord.
Wu
J V
JV
Department of Anesthesia, Stanford University School of Medicine, California 94305-5117, USA.
Kendig
J J
JJ
D000777:Anesthetics / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000187:drug effects* / Q000378:metabolism; D013116:Spinal Cord; D013779:Tetrodotoxin / Q000494:pharmacology*; D013997:Time Factors
D000777:Anesthetics; D015222:Sodium Channels; D000431:Ethanol; D013779:Tetrodotoxin; D012964:Sodium