Depolarization-dependent actions of dihydropyridines on synaptic transmission in the in vitro rat hippocampus.
Field potential and intracellular recordings were obtained in the in vitro hippocampal slice to study the effects on synaptic transmission of dihydropyridine (DHP) derivatives. Nimodipine or nifedipine by itself had little effect upon the postsynaptic response as determined by field potential analysis. However, facilitation became evident when DHP application was coupled with manipulations which induced a moderate degree of membrane depolarization. In accordance with the hydrophobic nature of these compounds, extensive washing in normal Krebs' solution failed to reverse the facilitation indicating that the DHP effects outlasted the induced depolarization. Nifedipine is photolabile and its actions were reversed when intense light was applied to the slice. Application of the DHP Bay K 8644, resulted in a similar depolarization-dependent increase in neuronal excitability which, upon washout and exposure to light, was at first attenuated and then reversed, resulting in a long-lasting depression of the EPSP that was sensitive to caffeine. This depressant action of Bay K 8644 appeared to be mediated at a site presynaptic to the pyramidal cell because the postsynaptic component of the field potential response to pulsed applications of glutamate was not altered. Intracellular recording from CA1 neurons supports a presynaptic locus for the depressant actions of Bay K 8644; spike threshold for synaptically evoked responses was greatly increased while spike threshold to direct depolarization of the soma was unchanged. These results indicate that DHPs can exert effects on synaptic transmission in hippocampal brain slice under conditions of moderate membrane depolarization.
Department of Neurology, Yale University School of Medicine, New Haven, CT.
M H
MH
O'Regan
J D
JD
Kocsis
S G
SG
Waxman
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D004095:Dihydropyridines / Q000494:pharmacology*; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008027:Light; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology; D009553:Nimodipine / Q000494:pharmacology; D010477:Perfusion; D011188:Potassium / Q000494:pharmacology; D011712:Pyramidal Tracts / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D013569:Synapses / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D009435:Synaptic Transmission / Q000187:drug effects* / Q000528:radiation effects
D004095:Dihydropyridines; D002110:Caffeine; D009553:Nimodipine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009543:Nifedipine; D011188:Potassium