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...

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Autores principales:	Piriz, J., Siri, M.D.R., Pagani, R., Uchitel, O.D.
Formato:	JOUR
Materias:	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
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_00223565_v306_n2_p658_Piriz
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

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spelling	todo:paper_00223565_v306_n2_p658_Piriz2023-10-03T14:31:57Z Nifedipine-mediated mobilization of intracellular calcium stores increases spontaneous neurotransmitter release at neonatal rat motor nerve terminals Piriz, J. Siri, M.D.R. Pagani, R. Uchitel, O.D. 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 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. Fil:Piriz, J. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Pagani, R. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Uchitel, O.D. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00223565_v306_n2_p658_Piriz
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	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
spellingShingle	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 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
topic_facet	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
description	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.
format	JOUR
author	Piriz, J. Siri, M.D.R. Pagani, R. Uchitel, O.D.
author_facet	Piriz, J. Siri, M.D.R. Pagani, R. Uchitel, O.D.
author_sort	Piriz, J.
title	Nifedipine-mediated mobilization of intracellular calcium stores increases spontaneous neurotransmitter release at neonatal rat motor nerve terminals
title_short	Nifedipine-mediated mobilization of intracellular calcium stores increases spontaneous neurotransmitter release at neonatal rat motor nerve terminals
title_full	Nifedipine-mediated mobilization of intracellular calcium stores increases spontaneous neurotransmitter release at neonatal rat motor nerve terminals
title_fullStr	Nifedipine-mediated mobilization of intracellular calcium stores increases spontaneous neurotransmitter release at neonatal rat motor nerve terminals
title_full_unstemmed	Nifedipine-mediated mobilization of intracellular calcium stores increases spontaneous neurotransmitter release at neonatal rat motor nerve terminals
title_sort	nifedipine-mediated mobilization of intracellular calcium stores increases spontaneous neurotransmitter release at neonatal rat motor nerve terminals
url	http://hdl.handle.net/20.500.12110/paper_00223565_v306_n2_p658_Piriz
work_keys_str_mv	AT pirizj nifedipinemediatedmobilizationofintracellularcalciumstoresincreasesspontaneousneurotransmitterreleaseatneonatalratmotornerveterminals AT sirimdr nifedipinemediatedmobilizationofintracellularcalciumstoresincreasesspontaneousneurotransmitterreleaseatneonatalratmotornerveterminals AT paganir nifedipinemediatedmobilizationofintracellularcalciumstoresincreasesspontaneousneurotransmitterreleaseatneonatalratmotornerveterminals AT uchitelod nifedipinemediatedmobilizationofintracellularcalciumstoresincreasesspontaneousneurotransmitterreleaseatneonatalratmotornerveterminals
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Nifedipine-mediated mobilization of intracellular calcium stores increases spontaneous neurotransmitter release at neonatal rat motor nerve terminals

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