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NEUROPHARMACOLOGY

Nifedipine-Mediated Mobilization of Intracellular Calcium Stores Increases Spontaneous Neurotransmitter Release at Neonatal Rat Motor Nerve Terminals

Laboratorio de Fisiología y Biología Molecular, Departamento de Fisiología y Biología Celular y Molecular and Instituto de Fisiología, Biología Molecular y Neurociencias-Consejo Nacional de Investigaciones Científicas y Técnicas, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina

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 µM. 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 µM thapsigargin and was partially inhibited by 10 µM 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.

Address correspondence to: Dr. Osvaldo D. Uchitel, Laboratorio de Fisiología y Biología Molecular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pab II 2^de piso, Buenos Aires 1428, Argentina. E-mail: odu{at}fibertel.com.ar

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