Increased susceptibility of brain slices from carbonic anhydrase II-deficient mice to low [Mg2+]O-induced seizures.
Brain pH is thought to be an influential factor in determining susceptibility to seizures. We compared the susceptibility of brain slices from carbonic anhydrase II (CA II)-deficient mice to epileptiform activity induced by low extracellular [Mg2+], with slices from normal littermates, both bathed in artificial cerebrospinal fluid at pH 7.3. In both entorhinal cortex and hippocampal field CA1, epileptiform activity started earlier in CA II-deficient slices. Raising extracellular [CO2] (20%; extracellular pH, 6.7) reversibly blocked the epileptiform activity in normal, but not in CA II-deficient, slices. The data, combined with previous in vivo findings showing an increased resistance of mutants to seizures, suggest the presence of in vivo anticonvulsant acidosis with long-term compensatory changes that lead to in vitro 'proconvulsant' behavior in CA II-deficient slices clamped at pH 7.3.
Velísek
L
L
Department of Neurology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. velisek@aecom.yu.edu
Moshé
S L
SL
Stanton
P K
PK
D000818:Animals; D001921:Brain / Q000187:drug effects*; D002256:Carbonic Anhydrases / Q000502:physiology*; D018728:Entorhinal Cortex / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects; D008274:Magnesium / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D011930:Reaction Time / Q000187:drug effects*; D012640:Seizures / Q000139:chemically induced*
D002256:Carbonic Anhydrases; D008274:Magnesium