Influence of stimulation on Ca(2+) recruitment triggering [3H]acetylcholine release from the rat motor-nerve endings.
The influence of rat phrenic nerve stimulation frequency (5-50 Hz) and of pulse duration (0.04-1 ms) on Ca(2+) mobilization triggering [3H]acetylcholine release was investigated. The P-type voltage-dependent Ca(2+) channel (VDCC) blocker, omega-agatoxin IVA (100 nM), decreased [3H]acetylcholine release evoked by pulses of 0. 04-ms duration delivered at 5 Hz frequency. When the stimulus pulse duration was increased to 1 ms (5 Hz frequency) or the stimulation frequency to 50 Hz (0.04-ms duration), inhibition of [3H]acetylcholine release became evident after blockade of L-type VDCC, with nifedipine (1 microM), and/or depletion of thapsigargin-sensitive internal stores. The inhibitory effect of thapsigargin (2 microM) was still observed in Ca(2+)-free medium. Neither omega-conotoxin GVIA (1 microM) nor omega-conotoxin MVIIC (150 nM) modified neurotransmitter release. The results suggest that, depending on the stimulus paradigm, both internal (thapsigargin-sensitive) and external (either P- or L-type channels) Ca(2+) pools can be mobilized to promote acetylcholine release from motor nerve terminals.
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Laboratório de Farmacologia, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS) - Universidade do Porto, L. Prof. Abel Salazar, 2, 4099-003, Porto, Portugal. farmacol@icbas.up.pt
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Ribeiro
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D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000187:drug effects; D005260:Female; D008297:Male; D009469:Neuromuscular Junction / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D019284:Thapsigargin / Q000494:pharmacology; D020867:omega-Agatoxin IVA / Q000494:pharmacology
D020746:Calcium Channels, L-Type; D020867:omega-Agatoxin IVA; D019284:Thapsigargin; D009543:Nifedipine; D000109:Acetylcholine; D002118:Calcium