3,4-Diaminopyridine-induced impairment in frog motor nerve terminal response to high frequency stimulation.
The refractory period of the presynaptic Na+ current (INa) of the frog neuromuscular junction before and after the block of the presynaptic delayed rectifier K+ conductance by 3,4-diaminopyridine (3,4-DAP) was studied by the perineurial recording technique. Application of 3,4-DAP 0.45 mM greatly prolonged the refractory period of the last nodes of Ranvier of frog motor axons. Suppression of the repetitive activity caused by 3,4-DAP by 3-aminobenzoic acid ethyl ester (tricaine) 0.46 mM (a local anesthetic) decreased the refractory period back towards normal values. These results indicate that 3,4-DAP impairs conduction of high frequency nerve impulses along the last nodes of Ranvier due to its block of presynaptic K+ conductance. The spontaneous activation of the most excitable, last nerve segments seemed to be the main factor causing such impairment. This phenomenon could explain in part the adverse motor effects shown by some patients treated with high doses of 3,4-DAP.
Miralles
F
F
Laboratori de Neurobiologia Cel.lular i Molecular, Departament de Biologia Cel.lular i Anatomia Patològica, Facultat de Medicina, Hospital de Bellvitge, Universitat de Barcelona, Barcelona, Spain.
Solsona
C
C
D015761:4-Aminopyridine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000077770:Amifampridine; D000818:Animals; D004553:Electric Conductivity; D004558:Electric Stimulation / Q000379:methods; D009046:Motor Neurons / Q000187:drug effects* / Q000502:physiology; D009469:Neuromuscular Junction / Q000502:physiology; D011188:Potassium / Q000037:antagonists & inhibitors / Q000502:physiology; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000502:physiology; D011898:Ranidae; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D012964:Sodium / Q000502:physiology
D012964:Sodium; D015761:4-Aminopyridine; D000077770:Amifampridine; D011188:Potassium