Control of epileptiform burst rate by CA3 hippocampal cell afterhyperpolarizations in vitro.
Spontaneous interictal bursts occurred at a high rate in rat hippocampal slices bathed in raised [K]o (7-10.5 mM) and at a slower rate in slices bathed in low [Cl]o (53 mM) solutions. Intracellular recordings from CA3b/c neurons bathed in high [K]o showed that the amplitude of the afterhyperpolarization that followed each spontaneous epileptiform burst varied -50 +/- 7 mV per decade change in [K]o (n = 7). Afterhyperpolarization duration was highly correlated with the interburst interval in 7-10.5 mM [K]o but not in low [Cl]o (3.5 mM [K]o). The duration of the afterhyperpolarization accounted for 79 +/- 2% of the interburst interval (1.4 +/- 0.1 s) in 8.5 mM [K]o but only 51 +/- 8% in low [Cl]o (interval 6.6 +/- 1.2 s). Treatment of slices bathed in 8.5 mM [K]o with phorbol 12,13-diacetate (2-20 microM) caused a decrease in the amplitude and duration of the afterhyperpolarization and a concomitant 41% increase in burst rate. In addition, spontaneous discharges that resembled the tonic phase of electrographic seizures appeared in the CA3 region. The GABAB receptor blocker phaclofen (0.2-1 mM) had no effect on the burst rate. We suggest that the epileptiform burst afterhyperpolarization limits the maximum rate of spontaneous interictal-like bursting and that a decrease in its duration allowed the subsequent expression of electrographic seizure activity in area CA3.
Chamberlin
N L
NL
Department of Pharmacology, University of North Carolina, Chapel Hill 27599-7365.
Dingledine
R
R
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology; D004827:Epilepsy / Q000503:physiopathology*; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D010703:Phorbol Esters / Q000494:pharmacology; D011188:Potassium / Q000502:physiology; D051381:Rats
D010703:Phorbol Esters; C052329:phaclofen; D001418:Baclofen; D011188:Potassium