Potassium channel activators counteract anoxic hyperexcitability but not 4-aminopyridine-induced epileptiform activity in the rat hippocampal slice.
The K+ channel activators diazoxide and cromakalim were investigated for effects on 4-aminopyridine (4AP)-induced epileptiform activity in adult rat hippocampal slices maintained in vitro. Under normal conditions of oxygenation, 4AP (50 microM) induced two types of field potentials in extracellular recordings from the CA3 stratum radiatum (apical dendritic region): epileptiform interictal discharge-like events occurring at a frequency of 0.75 +/- 0.36 Hz and long-lasting negative-going potentials mediated by GABA receptor activation that occurred at 0.03 +/- 0.01 Hz (n = 36 slices). Neither diazoxide (0.65-1.3 mM, n = 21 slices) nor cromakalim (50-200 microM, n = 6 slices) altered these two types of discharge. Brief periods of anoxia (4-6 min) reduced the frequency of the 4AP-induced interictal-like events (from 0.75 +/- 0.36 Hz to 0.19 +/- 0.15 Hz, n = 20 slices). In 45% of the experiments, the depressant effect of anoxia was preceded by a period of hyperexcitability consisting of a transient (36.1 +/- 12.9 sec) increase in the frequency of interictal-like events riding on a negative-going DC shift (n = 9 slices). Both responses to anoxia were reversible upon reoxygenation. In contrast, the rate of occurrence of the GABA-mediated potentials was unaffected by the anoxic episodes. Perfusion with cromakalim (n = 4 slices) or diazoxide (n = 5 slices) abolished the initial period of hyperexcitability produced by O2 deprivation but did not alter the subsequent depression of activity. Our experiments indicate that the K+ channel activators can prevent the initial hyperexcitability produced by anoxia, but do not influence 4AP-induced epileptiform activity in normoxic conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
Mattia
D
D
Montreal Neurological Institute, McGill University, QC, Canada.
Nagao
T
T
Rogawski
M A
MA
Avoli
M
M
D015761:4-Aminopyridine; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D019806:Cromakalim; D003981:Diazoxide / Q000494:pharmacology; D004827:Epilepsy / Q000139:chemically induced*; D006624:Hippocampus / Q000187:drug effects*; D002534:Hypoxia, Brain / Q000188:drug therapy*; D066298:In Vitro Techniques; D008297:Male; D015221:Potassium Channels / Q000819:agonists*; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D001578:Benzopyrans; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim; D015761:4-Aminopyridine; D003981:Diazoxide