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Abstract:

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 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 atherapeutic or a research tool.

Registro:

Documento: Artículo
Título:Nifedipine-mediated mobilization of intracellular calcium stores increases spontaneous neurotransmitter release at neonatal rat motor nerve terminals
Autor:Piriz, J.; Siri, M.D.R.; Pagani, R.; Uchitel, O.D.
Filiación:Depto. Fisiol. Biol. Cel. Molec., Instituto de Fisiología, Universidad de Buenos Aires, Buenos Aires, Argentina
Instituto Cajal, Consejo Sup. de Invest. Cientificas, Avenida Doctor Arce 37, 28002 Madrid, Spain
Biophysics Sector, Ist. Naz. di Fis. della Materia Unit, Intl. School for Advanced Studies, Via Beirut 2-4 (34014), Trieste, Italy
Lab. de Fisiol. y Biologia Molecular, Fac. de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Buenos Aires 1428, Argentina
Palabras clave:calciseptine; calcium channel blocking agent; calcium channel L type; calcium ion; isradipine; neurotransmitter; nifedipine; nitrendipine; omega agatoxin VIA; ryanodine; ryanodine receptor; thapsigargin; animal tissue; article; calcium cell level; calcium transport; concentration response; controlled study; diagnostic value; drug effect; drug mechanism; drug use; long term potentiation; miniature endplate potential; nerve ending; neuromuscular synapse; neurotransmitter release; newborn; nonhuman; priority journal; protein expression; rat; time series analysis; Age Factors; Animals; Calcium; Calcium Channel Blockers; Electrophysiology; Intracellular Fluid; Motor Endplate; Motor Neurons; Neurotransmitter Agents; Nifedipine; Rats; Rats, Sprague-Dawley
Año:2003
Volumen:306
Número:2
Página de inicio:658
Página de fin:663
DOI: http://dx.doi.org/10.1124/jpet.103.051524
Título revista:Journal of Pharmacology and Experimental Therapeutics
Título revista abreviado:J. Pharmacol. Exp. Ther.
ISSN:00223565
CODEN:JPETA
CAS:calciseptine, 134710-25-1; calcium ion, 14127-61-8; isradipine, 75695-93-1, 88977-22-4; nifedipine, 21829-25-4; nitrendipine, 39562-70-4; ryanodine, 15662-33-6; thapsigargin, 67526-95-8; Calcium Channel Blockers; Calcium, 7440-70-2; Neurotransmitter Agents; Nifedipine, 21829-25-4
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00223565_v306_n2_p658_Piriz

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Citas:

---------- APA ----------
Piriz, J., Siri, M.D.R., Pagani, R. & Uchitel, O.D. (2003) . Nifedipine-mediated mobilization of intracellular calcium stores increases spontaneous neurotransmitter release at neonatal rat motor nerve terminals. Journal of Pharmacology and Experimental Therapeutics, 306(2), 658-663.
http://dx.doi.org/10.1124/jpet.103.051524
---------- CHICAGO ----------
Piriz, J., Siri, M.D.R., Pagani, R., Uchitel, O.D. "Nifedipine-mediated mobilization of intracellular calcium stores increases spontaneous neurotransmitter release at neonatal rat motor nerve terminals" . Journal of Pharmacology and Experimental Therapeutics 306, no. 2 (2003) : 658-663.
http://dx.doi.org/10.1124/jpet.103.051524
---------- MLA ----------
Piriz, J., Siri, M.D.R., Pagani, R., Uchitel, O.D. "Nifedipine-mediated mobilization of intracellular calcium stores increases spontaneous neurotransmitter release at neonatal rat motor nerve terminals" . Journal of Pharmacology and Experimental Therapeutics, vol. 306, no. 2, 2003, pp. 658-663.
http://dx.doi.org/10.1124/jpet.103.051524
---------- VANCOUVER ----------
Piriz, J., Siri, M.D.R., Pagani, R., Uchitel, O.D. Nifedipine-mediated mobilization of intracellular calcium stores increases spontaneous neurotransmitter release at neonatal rat motor nerve terminals. J. Pharmacol. Exp. Ther. 2003;306(2):658-663.
http://dx.doi.org/10.1124/jpet.103.051524