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PMID: 8917594 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Ca(2+)-induced rebound potentiation of gamma-aminobutyric acid-mediated currents requires activation of Ca2+/calmodulin-dependent kinase II.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 93 ·No. 23 ·1996-11-12 ·Pages 13351-6

Kano M, Kano M, Fukunaga K, Konnerth A

Abstract

In cerebellar Purkinje neurons, gamma-aminobutyric acid (GABA)-mediated inhibitory synaptic transmission undergoes a long-lasting "rebound potentiation" after the activation of excitatory climbing fiber inputs. Rebound potentiation is triggered by the climbing-fiber-induced transient elevation of intracellular Ca2+ concentration and is expressed as a long-lasting increase of postsynaptic GABAA receptor sensitivity. Herein we show that inhibitors of the Ca2+/calmodulin-dependent protein kinase II (CaM-KII) signal transduction pathway effectively block the induction of rebound potentiation. These inhibitors have no effect on the once established rebound potentiation, on voltage-gated Ca2+ channel currents, or on the basal inhibitory transmission itself. Furthermore, a protein phosphatase inhibitor and the intracellularly applied CaM-KII markedly enhanced GABA-mediated currents in Purkinje neurons. Our results demonstrate that CaM-KII activation and the following phosphorylation are key steps for rebound potentiation.

MeSH Terms
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/analogs & derivatives,pharmacology Animals Calcium/pharmacology Calcium-Calmodulin-Dependent Protein Kinase Type 2 Calcium-Calmodulin-Dependent Protein Kinases/antagonists & inhibitors,metabolism Cerebellum/enzymology,physiology Drug Synergism Enzyme Activation Enzyme Inhibitors/pharmacology Imidazoles/pharmacology In Vitro Techniques Kinetics Marine Toxins Membrane Potentials/drug effects Nerve Fibers/drug effects,physiology Oxazoles/pharmacology Purkinje Cells/drug effects,enzymology,physiology Rats Receptors, GABA-A/physiology Signal Transduction Staurosporine/pharmacology gamma-Aminobutyric Acid/pharmacology
Chemicals
Enzyme Inhibitors Imidazoles Marine Toxins Oxazoles Receptors, GABA-A calmidazolium gamma-Aminobutyric Acid KN 62 calyculin A 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine Calcium-Calmodulin-Dependent Protein Kinase Type 2 Calcium-Calmodulin-Dependent Protein Kinases Staurosporine Calcium
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Kano M
Department of Physiology, Jichi Medical School, Tochigi, Japan. [email protected]
Kano M
Fukunaga K
Konnerth A
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.93.23.13351
Email
[email protected]
Published
1996-11-12
Pages
13351-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC24096
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.93.23.13351 PMC Full Text View journal details
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