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PMID: 7473240 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Ryanodine receptor-mediated intracellular calcium release in rat cerebellar Purkinje neurones.

The Journal of physiology ·Vol. 487 ·No. 1 ·1995-08-15 ·Pages 1-16

Kano M, Garaschuk O, Verkhratsky A, Konnerth A

Abstract

1. Ryanodine receptor-mediated Ca2+ release was investigated in Purkinje neurones of rat cerebellar slices by using whole-cell patch-clamp recordings combined with fluorometric digital imaging of cytoplasmic Ca2+ concentration ([Ca2+]i). 2. Caffeine caused a transient increase in [Ca2+]i in the somata and dendrites of Purkinje neurones. Caffeine-induced Ca2+ transients were not associated with a membrane inward current and persisted in Ca(2+)-free external solutions, indicating that they are caused by Ca2+ released from intracellular stores. The amplitudes of the caffeine-mediated elevations in [Ca2+]i were strongly dependent on the baseline level of [Ca2+]i. 3. Intracellular application of Ruthenium Red through the patch pipette blocked caffeine-induced Ca2+ transients in Purkinje neurones. Ryanodine when applied either intra- or extracellularly caused a use-dependent block of caffeine-induced Ca2+ release. 4. Depolarization-induced Ca2+ transients were strongly prolonged by caffeine. Several lines of evidence suggest that these prolongations reflect Ca(2+)-induced Ca2+ release. 5. Despite the presence of skeletal muscle type ryanodine receptors in Purkinje neurones, depolarizing pulses failed to induce any changes in [Ca2+]i when the influx of Ca2+ through voltage-gated channels was prevented by using Ca(2+)-free solution, or when applying blockers of voltage-gated Ca2+ channels. 6. Dendritic Ca2+ transients produced by stimulation of the excitatory climbing fibre synaptic input were also prolonged by caffeine, indicating that ryanodine receptor-mediated release of Ca2+ may be involved in synaptic signalling in cerebellar Purkinje neurones. 7. Ryanodine receptor-mediated release of Ca2+ in cerebellar Purkinje neurones can be explained by a model in which release of Ca2+ is strongly facilitated by the co-operative action of Ca2+, caffeine and/or ryanodine. Our results suggest that Ca2+ release in these central neurones becomes prominent only during episodes of intensive electrical activity associated with increased Ca2+ entry.

MeSH Terms
Animals Caffeine/antagonists & inhibitors,pharmacology Calcium/metabolism,physiology Calcium Channel Blockers/pharmacology Calcium Channels/physiology Electrophysiology Fluorometry Intracellular Membranes/metabolism Muscle Proteins/physiology Nerve Fibers/physiology Patch-Clamp Techniques Phosphodiesterase Inhibitors/pharmacology Purkinje Cells/metabolism Rats Rats, Wistar Reaction Time Ruthenium Red/pharmacology Ryanodine/pharmacology Ryanodine Receptor Calcium Release Channel Synapses/physiology
Chemicals
Calcium Channel Blockers Calcium Channels Muscle Proteins Phosphodiesterase Inhibitors Ryanodine Receptor Calcium Release Channel Ruthenium Red Ryanodine Caffeine Calcium
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Kano M
I. Physiologisches Institut, Universität des Saarlandes, Homburg, Germany.
Garaschuk O
Verkhratsky A
Konnerth A
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Article Info
Journal
The Journal of physiology
Abbr.
J Physiol
ISSN
0022-3751
Published
1995-08-15
Pages
1-16
Language
English
Region
England
NLM ID
0266262
PMCID
PMC1156595
Subset
IM
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