Hyperthermic spreading depressions in the immature rat hippocampal slice.
Febrile seizures are the most common seizure type in children (6 mo to 5 yr). The pathophysiology of febrile seizures is unknown. Current genetic studies show that some febrile seizures result from channelopathies. We have performed electrophysiological experiments in in vitro hippocampal slices to test a novel hypothesis that a disordered regulation of ionic homeostasis underlies the genesis of febrile seizures. In transverse hippocampal CA1 slices from 104 rats, temperature increase from 34 degrees to 40 degrees C produced a series of spreading depressions (SDs), called hyperthermic SDs. The hyperthermic SDs were age-dependent, occurring in only 1/17 8-16 day-old animals, 44/49 17-60 day-old animals, and 11/20 rats older than than 60 days. The hyperthermic SDs usually occurred on the rising phase of the temperature. The mean temperature to trigger a first hyperthermic SD was 38.8 +/- 1.3 degrees C (mean +/- SD, n = 44). The hyperthermic SDs induced a reversible loss of evoked synaptic potentials and a dramatic decrease of input resistance. Neuronal and field epileptiform bursting occurred in the early phases of the hyperthermic SD. During hyperthermic SDs, pyramidal cell membrane potential depolarized by 38.3 +/- 4.9 mV (n = 20), extracellular field shifted negative 18.5 +/- 3.9 mV (n = 44), and extracellular K(+) rose reversibly to 43.8 +/- 10.9 mM (n = 6). Similar SDs could be evoked by ouabain or transient hypoxia with normal temperature. Tetrodotoxin could block initial epileptiform bursting, without blocking SDs. Hyperthermia-induced SDs should be investigated as possible contributing factors to febrile seizures.
Wu
J
J
Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona 85013-4496, USA.
Fisher
R S
RS
D000200:Action Potentials / Q000502:physiology; D000375:Aging / Q000502:physiology*; D000818:Animals; D013181:Cortical Spreading Depression / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005110:Extracellular Space / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D006979:Hyperthermia, Induced; D066298:In Vitro Techniques; D008839:Microelectrodes; D010477:Perfusion; D011188:Potassium / Q000378:metabolism; D051381:Rats; D003294:Seizures, Febrile / Q000209:etiology*; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin / Q000494:pharmacology
D026941:Sodium Channel Blockers; D013779:Tetrodotoxin; D011188:Potassium