Nifedipine-mediated mobilization of intracellular calcium stores increases spontaneous neurotransmitter release at neonatal rat motor nerve terminals.
The modulation of spontaneous release of acetylcholine by specific Ca2+ channel blockers was studied at neonatal rat neuromuscular junction. During early postnatal periods (0-4 days), blockers of N- and P/Q-type Ca2+ channels did not affect miniature endplate potential (MEPP) frequency. Unexpectedly, treatment with the L-type Ca2+ channel antagonist nifedipine, although not when treated with isradipine, nitrendipine, or calciseptine, resulted in strong increase in MEPP frequency. The potentiation effect of nifedipine was dose-dependent with a 56-fold maximum effect with 15 microM. The effect decreased during the first two postnatal weeks and disappeared by the third. The effect of nifedipine was not dependent on extracellular Ca2+ and was not altered by the presence of other Ca2+ channel blockers. In contrast, it was abolished by depleting intracellular Ca2+ stores with 2 microM thapsigargin and was partially inhibited by 10 microM ryanodine. In conclusion, we report a new ryanodine receptor-mediated effect of nifedipine on neonatal neuromuscular junction that may indicate the developmental expression of a specific receptor channel that interacts with intracellular Ca2+ stores. This effect of nifedipine should also be considered when using this drug as either a therapeutic or a research tool.
Piriz
J
J
Departamento de Fisiología y Biología Celular y Molecular, Universidad de Buenos Aires, Ciudad Universitaria, Buenos Aires, Argentina.
Rosato Siri
M D
MD
Pagani
R
R
Uchitel
O D
OD
D000367:Age Factors; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004594:Electrophysiology; D066298:In Vitro Techniques; D007424:Intracellular Fluid; D009045:Motor Endplate / Q000187:drug effects* / Q000378:metabolism; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002121:Calcium Channel Blockers; D018377:Neurotransmitter Agents; D009543:Nifedipine; D002118:Calcium