A comparison of the effects of pentobarbital and diphenylhydantoin on the GABA sensitivity and excitability of adult sensory ganglion cells.
The actions of pentobarbital (PB) and diphenylhydantoin (DPH) have been studied on neurons of dorsal root ganglia from adult rats. At anesthetic level (i.e. 1--2 x 10(-4) M), PB greatly enhanced neuronal responses to gamma-aminobutyric acid (GABA); at 10(-3) M PB caused a small depolarization and profoundly attenuated GABA responses, probably because of cross-desensitization of GABA receptors. In contrast to results in some non-mammalian species, DPH (up to 2 x 10(-4) M) did not affect GABA responses under any conditions. PB depressed single intracellularly evoked action potentials only at high concentrations, but the cell's ability to fire trains of impulses in response to prolonged depolarization was impaired (i.e. accommodation was enhanced) at the anesthetic dosage level. DPH (1--2 x 10(-4) M) selectively depressed sodium-dependent action potentials of tetrodotoxin (TTX)-sensitive cells, and also impaired their ability to fire repetitively, but it did not influence sodium conductances and other aspects of excitability of TTX-insensitive neurons. In addition, both DPH and TTX reversed neuronal depolarizations induced by veratridine. Calcium-dependent potentials appeared to be unaltered by DPH. The results suggest that the anesthetic properties of PB may depend, in part, upon the enhancement of GABA-mediated inhibitions and increased accommodation. The anticonvulsant DPH exerts a selective, TTX-like depression of sodium conductances which does not extend to sodium conductances which are insensitive to TTX.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005071:Evoked Potentials / Q000187:drug effects; D005727:Ganglia, Spinal / Q000187:drug effects*; D007473:Ion Channels / Q000187:drug effects; D010424:Pentobarbital / Q000494:pharmacology*; D010672:Phenytoin / Q000494:pharmacology*; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects*; D011963:Receptors, GABA-A; D013779:Tetrodotoxin / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D007473:Ion Channels; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D010672:Phenytoin; D014701:Veratridine; D010424:Pentobarbital