Frequency- and structure-dependent inhibition of normal and epileptiform activity by 6-benzoyldeltamine in rat hippocampal slices.
The present study investigated the effects of the Aconitum alkaloids 6-benzoyldeltamine and the structurally related eldeline on neuronal activity in rat hippocampal slices. 6-Benzoyldeltamine (1-30 microM) decreased the orthodromic field potentials recorded in area CA1 in a concentration-dependent manner. The inhibitory effect of eldeline (3-100 microM) was lower. The attenuation of the postsynaptic population spike was accompanied by a simultaneous decrease in the presynaptic fibre spike evoked by electrical stimulation of the Schaffer collaterals. The input-output relationship of the presynaptic fibre spike as function of the stimulation intensity, and for the postsynaptic population spike as function of the presynaptic fibre spike was shifted to the right. Thus, electrophysiologically, these alkaloids seem to inhibit predominantly the excitability of the afferent fibres and, in consequence, neurotransmission between Schaffer collaterals and the CAI neurons, thereby suppressing the firing of the latter. The inhibitory action of 6-benzoyldeltamine revealed use-dependence as obvious by an enhanced attenuation of the antidromic spike when stimulation frequency was increased. 6-Benzoyldeltamine inhibited stimulus-triggered epileptiform population bursts in area CA1 elicited by omission of Mg2+, as well as spontaneously occurring epileptiform discharges in area CA3 elicited by omission of Mg2+ and elevation of K+. Complete suppression of spontaneous activity was observed at 1 microM 6-benzoyldeltamine, which reduced the population spike only by about 20% of control. It is concluded that the inhibitory and antiepileptiform effect of 6-benzoyldeltamine is mediated by a frequency-dependent decrease in excitability, which might be important for filtering high frequency bursts of action potentials characteristic for epileptiform activity in the hippocampus.
Ameri
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Institute of Pharmacology, Toxicology and Natural Products, University of Ulm, Germany.
Zimmermann
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T
Simmet
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T
D000157:Aconitine / Q000031:analogs & derivatives; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D046508:Culture Techniques; D004224:Diterpenes / Q000494:pharmacology*; D004347:Drug Interactions; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects*; D008278:Magnesium Sulfate / Q000494:pharmacology; D008297:Male; D008839:Microelectrodes; D009475:Neurons, Afferent / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D015149:Tocolytic Agents / Q000494:pharmacology
C119643:6-benzoyldeltamine; D000470:Alkaloids; D000927:Anticonvulsants; D004224:Diterpenes; D016194:Receptors, N-Methyl-D-Aspartate; D015149:Tocolytic Agents; C119644:eldeline; D008278:Magnesium Sulfate; D000157:Aconitine