Effects of dihydropyridines on calcium currents in CA3 pyramidal cells in slice cultures of rat hippocampus.
Slow inward Ca-currents were recorded from CA3 pyramidal cells in rat hippocampus slice cultures when these cells were voltage-clamped at -40 mV and depolarizing commands applied. Ca-currents were increased in amplitude by the dihydropyridine Ca-agonist BAY K8644 (0.1-1 microM) and reduced by the Ca-antagonists nifedipine and PY 108-068 (0.1-1 microM). Ca-current inhibition by the latter could be temporarily relieved by membrane hyperpolarization. In unclamped cells, dihydropyridines did not alter membrane potential, Ca-spike amplitude, excitatory or inhibitory synaptic current amplitude, or spontaneous synaptic activity. Their principal effects were to alter the threshold for Ca/Ba spike generation and for pitrazepin-induced burst-depolarization. BAY K8644 also induced an after-spike following the normal Na spike, which was reduced by PY 108-068. It is concluded that the slow inward Ca-current in hippocampal neurones is sensitive to dihydropyridine drugs and that the absence of functional effects of antagonists is due to other causes such as the voltage-dependence of dihydropyridine block and the presence of an additional transient Ca-current which may be less sensitive to block.
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D004553:Electric Conductivity; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats
D002104:Cadmium; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009543:Nifedipine; C034600:darodipine; D002118:Calcium