Effects of antiepileptic drugs on extracellular pH regulation in the hippocampal CA1 region in vivo.
Intracellular and extracellular pH are known to influence neuronal activity and may play a role in seizure termination. In the pyramidal cell layer of the CA1 region of the hippocampus in the urethane anesthetized adult rat, there is an initial alkalinization in response to stimulus trains administered to the contralateral CA3 region. This is followed by an acidification that peaks after termination of the afterdischarge. Initial experiments demonstrated that the peak level of acidification correlated with the duration of the afterdischarge, but that the peak level of alkalinization did not. The effects of several antiepileptic drugs on the initial alkalinization were determined. Systemic administration of acetazolamide (50 mg/kg, n=4) and topiramate (45 mg/kg, n=7) and local administration of benzolamide (n=3), all of which inhibit carbonic anhydrase, decreased the initial alkalinization that occurs during the stimulus train. Diazepam (3 mg/kg, n=5) and phenobarbital (60 mg/kg, n=6), agonists at the GABA(A) receptor complex, increased the initial alkalinization, while sodium channel blockers phenytoin (80 mg/kg, n=5) and carbamazepine (50 mg/kg, n=5) had no significant effect. The data suggest that the alkalinization in CA1 in vivo is predominantly regulated through activity of the GABA(A) receptor, rather than through activation of glutamatergic receptors. The change in alkalinization does not appear to be related to the mechanism of the antiepileptic effect of the drugs that were tested.
Aribi
Ahmed M
AM
Department of Pharmacology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030-3498, USA.
Stringer
Janet L
JL
D000086:Acetazolamide / Q000494:pharmacology; D000468:Alkalies / Q000378:metabolism; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism*; D005632:Fructose / Q000031:analogs & derivatives / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration / Q000187:drug effects*; D008297:Male; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000502:physiology; D000077236:Topiramate
D000468:Alkalies; D000927:Anticonvulsants; D002257:Carbonic Anhydrase Inhibitors; D058785:GABA-A Receptor Agonists; D011963:Receptors, GABA-A; D000077236:Topiramate; D005632:Fructose; D000086:Acetazolamide; D003975:Diazepam; D010634:Phenobarbital