Ionic basis of inhibitory presynaptic modulation in rat cortical synaptosomes.
We have investigated the possibility that, regardless of the involvement of a second messenger system, the ultimate effect of presynaptic, receptor-activated inhibitory modulation is the opening of a K channel. With the consequent hyperpolarization of the terminal, less Ca2+ would enter and this would result in the observed diminished release of a neurotransmitter. This possibility was explored utilizing rat cortical synaptosomes that were prelabeled with either 86Rb or [3H]acetylcholine, depolarizing with either K+ or veratridine, and measuring either efflux of 86Rb or release of [3H]acetylcholine in the presence or absence of inhibitory presynaptic modulators. The modulating agents used were 2-chloroadenosine, carbamylcholine, clonidine, and morphine. In all instances, these agents promoted an increased efflux of 86Rb, indicating hyperpolarization, and decreased release of acetylcholine. These results are compatible with our suggestion that an increase in K conductance may be responsible for presynaptic inhibition of the release of neurotransmitters.
Zoltay
G
G
Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510.
Cooper
J R
JR
D015762:2-Chloroadenosine / Q000494:pharmacology; D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002540:Cerebral Cortex / Q000502:physiology*; D003000:Clonidine / Q000494:pharmacology; D009020:Morphine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012414:Rubidium Radioisotopes / Q000378:metabolism; D013569:Synapses / Q000502:physiology*; D013574:Synaptosomes / Q000187:drug effects / Q000502:physiology*; D014701:Veratridine / Q000494:pharmacology
D015221:Potassium Channels; D012414:Rubidium Radioisotopes; D015762:2-Chloroadenosine; D014701:Veratridine; D009020:Morphine; D002217:Carbachol; D003000:Clonidine; D000109:Acetylcholine; D011188:Potassium