Differential effects of 4-aminopyridine on acetylcholine release triggered by K+ depolarization, veratridine, or A23187 in rat cerebral cortical synaptosomes.
The effect of 4-aminopyridine on [3H]acetylcholine release was studied in rat cerebral cortical synaptosomes in the presence of a several secretagogues that have different mechanisms of action. As found previously, 4-aminopyridine increased [3H]acetylcholine release in a concentration-dependent manner (5-10 mM); a high concentration (10 mM) also elevated [3H]choline efflux. However, the 35 mM K+ induced release of [3H]acetylcholine was attenuated by 4-aminopyridine at concentrations (less than 5 mM) that had no effect on transmitter release. At no concentration of 4-aminopyridine was the release of transmitter additive with 35 mM K+ induced release. Veratridine-induced release was neither attenuated nor additive with low concentrations of 4-aminopyridine, even when a sub-maximal concentration of the sodium ionophore was used (10 microM). In contrast, A23187-induced release was additive with that caused by 4-aminopyridine. These results suggest that: 1) 4-aminopyridine blocks potassium channels involved in regulating membrane potential in isolated cholinergic terminals; and 2) changes in the activity of these 4-aminopyridine sensitive K+ channels are not important in the nerve terminal's response to depolarization caused by sodium influx.
Meyer
E M
EM
Department of Pharmacology and Experimental Therapeutics, University of Florida College of Medicine, Gainesville 32610.
Otero
D H
DH
D015761:4-Aminopyridine; D000109:Acetylcholine / Q000378:metabolism*; D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D014701:Veratridine / Q000494:pharmacology*; D014702:Veratrine / Q000031:analogs & derivatives*
D000631:Aminopyridines; D002800:Cholinesterase Inhibitors; D000001:Calcimycin; D014701:Veratridine; D015761:4-Aminopyridine; D014702:Veratrine; D000109:Acetylcholine; D011188:Potassium