Synaptic facilitation by 3-aminopyridine and its antagonism by verapamil and diltiazem.
The effects of 3-aminopyridine (3-AP) on synaptic transmission in bullfrog sympathetic ganglion were studied in normal Ringer's solution and during graded reductions in extracellular Ca++ by means of intra- and extracellular recording techniques. 3-AP caused a single orthodromic stimulus to generate a brief burst of repetitive postganglionic discharges (SBR). In the absence of 3-AP, synaptic transmission, measured as the amplitude of the postganglionic compound action potential, failed progressively as Ca++ was reduced from 1.8 to 0.47 mM. This Ca++ dependence curve of synaptic transmission was shifted to the left (lower Ca++) by 3-AP in dose-related fashion, with maximum shift (4- to 5-fold) at 1 mM 3-AP. The magnitude of the maximum shift produced by 3-AP was precisely the same as that produced by 3,4-diaminopyridine and 4-aminopyridine. Although 3-AP could prevent transmission failure at otherwise suboptimal Ca++ levels, its ability to generate SBR failed progressively as Ca++ was reduced from normal (1.8 mM) to 0.5 mM. Thus, there was a wide difference between the Ca++ dependence domains of synaptic transmission and of SBR in the presence of 3-AP. To confirm this difference in Ca++ dependence domains by a method other than reduction of [Ca++]0, we investigated the interactions between 3-AP and two Ca++ entry blockers, verapamil and diltiazem. 3-AP SBR was abolished by verapamil and by diltiazem at concentrations significantly below those required to block synaptic transmission in the presence of 3-AP. The results thus demonstrate a competitive interaction between aminopyridines and Ca++ entry blockers and further confirm the Ca++ dependent nature of the synaptic actions of aminopyridines.
D015761:4-Aminopyridine; D000200:Action Potentials / Q000187:drug effects; D000077770:Amifampridine; D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D004110:Diltiazem / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D011892:Rana catesbeiana; D013569:Synapses / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology*
D000631:Aminopyridines; D001552:Benzazepines; C031283:3-aminopyridine; D015761:4-Aminopyridine; D014700:Verapamil; D004110:Diltiazem; D000077770:Amifampridine; D002118:Calcium