TY - JOUR T1 - Nifedipine-Mediated Mobilization of Intracellular Calcium Stores Increases Spontaneous Neurotransmitter Release at Neonatal Rat Motor Nerve Terminals JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 658 LP - 663 DO - 10.1124/jpet.103.051524 VL - 306 IS - 2 AU - J. Piriz AU - M. D. Rosato Siri AU - R. Pagani AU - O. D. Uchitel Y1 - 2003/08/01 UR - http://jpet.aspetjournals.org/content/306/2/658.abstract N2 - 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. The American Society for Pharmacology and Experimental Therapeutics ER -