Organic and inorganic calcium antagonists inhibit veratridine-induced epileptiform activity in CA3 neurons of the guinea pig.
Veratridine is believed to cause epileptiform discharges via its effects on sodium channels. We addressed the question whether calcium currents, known to contribute to the generation of paroxysmal depolarization shifts (PDS) in most models of epilepsies, also contribute to veratridine-induced epileptiform activity. Therefore, we recorded from CA3 neurons (n=50) of veratridine-treated hippocampal slices and analyzed the effects of two calcium antagonists. Veratridine (0.5-1.0 microM) elicited spontaneous epileptiform bursts, paroxysmal depolarization shifts (PDS) lasting 100-300 ms, and depolarizations (LD) lasting up to several minutes. Most often PDS directly preceded LD which resulted in typical composite depolarizations termed veratridine-induced complexes (VC). VC persisted even in the presence of CNQX and APV (25 micromol/l, both), or in nominally calcium-free saline, revealing the non-synaptic nature of these potentials. Cobalt (1-2mM) abolished VC within minutes, but allowed LD type-like potentials to be elicited by depolarizing current pulses. Verapamil (50 microM) also diminished or abolished amplitudes of VC. All inhibitory effects of cobalt and verapamil were at least partly reversible. Due to the effects of both calcium antagonists we conclude that veratridine-induced epileptiform activity depends not only on sodium, but also on calcium currents.
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Mark Christian
MC
Institute of Physiology, University of Duisburg-Essen, Hufelandstr. 55, 45122 Essen, Germany.
Wiemann
Martin
M
Bingmann
Dieter
D
D000818:Animals; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003035:Cobalt / Q000494:pharmacology; D003292:Convulsants / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D004827:Epilepsy / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control*; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology*; D066298:In Vitro Techniques; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D014700:Verapamil / Q000494:pharmacology; D014701:Veratridine / Q000037:antagonists & inhibitors* / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D003292:Convulsants; D003035:Cobalt; D014701:Veratridine; D014700:Verapamil; D002118:Calcium