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A Ca(2+)-induced Ca(2+) Release Mechanism Involved in Asynchronous Exocytosis at Frog Motor Nerve Terminals

The extent to which Ca(2+)-induced Ca(2+) release (CICR) affects transmitter release is unknown. Continuous nerve stimulation (20–50 Hz) caused slow transient increases in miniature end-plate potential (MEPP) frequency (MEPP-hump) and intracellular free Ca(2+) ([Ca(2+)](i)) in presynaptic terminals...

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Autores principales: Narita, K., Akita, T., Osanai, M., Shirasaki, T., Kijima, H., Kuba, K.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1998
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2229444/
https://www.ncbi.nlm.nih.gov/pubmed/9806968
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author Narita, K.
Akita, T.
Osanai, M.
Shirasaki, T.
Kijima, H.
Kuba, K.
author_facet Narita, K.
Akita, T.
Osanai, M.
Shirasaki, T.
Kijima, H.
Kuba, K.
author_sort Narita, K.
collection PubMed
description The extent to which Ca(2+)-induced Ca(2+) release (CICR) affects transmitter release is unknown. Continuous nerve stimulation (20–50 Hz) caused slow transient increases in miniature end-plate potential (MEPP) frequency (MEPP-hump) and intracellular free Ca(2+) ([Ca(2+)](i)) in presynaptic terminals (Ca(2+)-hump) in frog skeletal muscles over a period of minutes in a low Ca(2+), high Mg(2+) solution. Mn(2+) quenched Indo-1 and Fura-2 fluorescence, thus indicating that stimulation was accompanied by opening of voltage-dependent Ca(2+) channels. MEPP-hump depended on extracellular Ca(2+) (0.05–0.2 mM) and stimulation frequency. Both the Ca(2+)- and MEPP-humps were blocked by 8-(N,N-diethylamino)octyl3,4,5-trimethoxybenzoate hydrochloride (TMB-8), ryanodine, and thapsigargin, but enhanced by CN(−). Thus, Ca(2+)-hump is generated by the activation of CICR via ryanodine receptors by Ca(2+) entry, producing MEPP-hump. A short interruption of tetanus (<1 min) during MEPP-hump quickly reduced MEPP frequency to a level attained under the effect of TMB-8 or thapsigargin, while resuming tetanus swiftly raised MEPP frequency to the previous or higher level. Thus, the steady/equilibrium condition balancing CICR and Ca(2+) clearance occurs in nerve terminals with slow changes toward a greater activation of CICR (priming) during the rising phase of MEPP-hump and toward a smaller activation during the decay phase. A short pause applied after the end of MEPP- or Ca(2+)-hump affected little MEPP frequency or [Ca(2+)](i), but caused a quick increase (faster than MEPP- or Ca(2+)-hump) after the pause, whose magnitude increased with an increase in pause duration (<1 min), suggesting that Ca(2+) entry-dependent inactivation, but not depriming process, explains the decay of the humps. The depriming process was seen by giving a much longer pause (>1 min). Thus, ryanodine receptors in frog motor nerve terminals are endowed with Ca(2+) entry-dependent slow priming and fast inactivation mechanisms, as well as Ca(2+) entry-dependent activation, and involved in asynchronous exocytosis. Physiological significance of CICR in presynaptic terminals was discussed.
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spelling pubmed-22294442008-04-22 A Ca(2+)-induced Ca(2+) Release Mechanism Involved in Asynchronous Exocytosis at Frog Motor Nerve Terminals Narita, K. Akita, T. Osanai, M. Shirasaki, T. Kijima, H. Kuba, K. J Gen Physiol Article The extent to which Ca(2+)-induced Ca(2+) release (CICR) affects transmitter release is unknown. Continuous nerve stimulation (20–50 Hz) caused slow transient increases in miniature end-plate potential (MEPP) frequency (MEPP-hump) and intracellular free Ca(2+) ([Ca(2+)](i)) in presynaptic terminals (Ca(2+)-hump) in frog skeletal muscles over a period of minutes in a low Ca(2+), high Mg(2+) solution. Mn(2+) quenched Indo-1 and Fura-2 fluorescence, thus indicating that stimulation was accompanied by opening of voltage-dependent Ca(2+) channels. MEPP-hump depended on extracellular Ca(2+) (0.05–0.2 mM) and stimulation frequency. Both the Ca(2+)- and MEPP-humps were blocked by 8-(N,N-diethylamino)octyl3,4,5-trimethoxybenzoate hydrochloride (TMB-8), ryanodine, and thapsigargin, but enhanced by CN(−). Thus, Ca(2+)-hump is generated by the activation of CICR via ryanodine receptors by Ca(2+) entry, producing MEPP-hump. A short interruption of tetanus (<1 min) during MEPP-hump quickly reduced MEPP frequency to a level attained under the effect of TMB-8 or thapsigargin, while resuming tetanus swiftly raised MEPP frequency to the previous or higher level. Thus, the steady/equilibrium condition balancing CICR and Ca(2+) clearance occurs in nerve terminals with slow changes toward a greater activation of CICR (priming) during the rising phase of MEPP-hump and toward a smaller activation during the decay phase. A short pause applied after the end of MEPP- or Ca(2+)-hump affected little MEPP frequency or [Ca(2+)](i), but caused a quick increase (faster than MEPP- or Ca(2+)-hump) after the pause, whose magnitude increased with an increase in pause duration (<1 min), suggesting that Ca(2+) entry-dependent inactivation, but not depriming process, explains the decay of the humps. The depriming process was seen by giving a much longer pause (>1 min). Thus, ryanodine receptors in frog motor nerve terminals are endowed with Ca(2+) entry-dependent slow priming and fast inactivation mechanisms, as well as Ca(2+) entry-dependent activation, and involved in asynchronous exocytosis. Physiological significance of CICR in presynaptic terminals was discussed. The Rockefeller University Press 1998-11-01 /pmc/articles/PMC2229444/ /pubmed/9806968 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Narita, K.
Akita, T.
Osanai, M.
Shirasaki, T.
Kijima, H.
Kuba, K.
A Ca(2+)-induced Ca(2+) Release Mechanism Involved in Asynchronous Exocytosis at Frog Motor Nerve Terminals
title A Ca(2+)-induced Ca(2+) Release Mechanism Involved in Asynchronous Exocytosis at Frog Motor Nerve Terminals
title_full A Ca(2+)-induced Ca(2+) Release Mechanism Involved in Asynchronous Exocytosis at Frog Motor Nerve Terminals
title_fullStr A Ca(2+)-induced Ca(2+) Release Mechanism Involved in Asynchronous Exocytosis at Frog Motor Nerve Terminals
title_full_unstemmed A Ca(2+)-induced Ca(2+) Release Mechanism Involved in Asynchronous Exocytosis at Frog Motor Nerve Terminals
title_short A Ca(2+)-induced Ca(2+) Release Mechanism Involved in Asynchronous Exocytosis at Frog Motor Nerve Terminals
title_sort ca(2+)-induced ca(2+) release mechanism involved in asynchronous exocytosis at frog motor nerve terminals
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2229444/
https://www.ncbi.nlm.nih.gov/pubmed/9806968
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