Pre- and postsynaptic actions of nifedipine at an identified cholinergic central synapse of Aplysia.
The effects of the dihydropyridine (DHP) Ca2+ channel antagonist, nifedipine, were studied on the cholinergic synapse between the presynaptic neurones B4/B5 and the postsynaptic neurones B3/B6 located in the buccal ganglion of Aplysia californica. Nifedipine (10 microM) decreased the presynaptic Ca2+ current by 30%-40%. Blockade of DHP-sensitive Ca2+ channels, however, did not affect quantal transmitter release from the presynaptic neurones. Thus, at this synapse, DHP-sensitive Ca2+ channels appear not to be involved in acetylcholine (ACh) release. The postsynaptic response to an ionophoretic application of ACh was decreased by nifedipine, pointing to a blocking action of the drug on the postsynaptic receptor/channel complex. Nifedipine was also found to activate protein kinase C, which in turn induces an increase in the nifedipine-resistant presynaptic Ca2+ influx and in the number of released ACh quanta. These effects of nifedipine could be prevented by a previous application of 1,5-(isoquinolinylsulfonyl)-2-methyl-piperazine (H-7), a protein kinase blocker.
Laboratoire de Neurobiologie Cellulaire et Moléculaire, C.N.R.S., Gif-sur-Yvette, France.
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D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001048:Aplysia; D002118:Calcium / Q000502:physiology; D002610:Cheek / Q000294:innervation; D004553:Electric Conductivity; D005726:Ganglia, Parasympathetic / Q000502:physiology*; D007546:Isoquinolines / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D013569:Synapses / Q000187:drug effects*
D007546:Isoquinolines; D018377:Neurotransmitter Agents; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D009543:Nifedipine; D000109:Acetylcholine; D002118:Calcium