title: Ca(2+)-induced rebound potentiation of gamma-aminobutyric acid-mediated currents requires activation of Ca2+/calmodulin-dependent kinase II.
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.
authors.affiliation: Department of Physiology, Jichi Medical School, Tochigi, Japan. mkano@postman.riken.go.jp
authors.forename: M
authors.initials: M
authors.lastname: Kano
authors.forename: M
authors.initials: M
authors.lastname: Kano
authors.forename: K
authors.initials: K
authors.lastname: Fukunaga
authors.forename: A
authors.initials: A
authors.lastname: Konnerth
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002531:Cerebellum / Q000201:enzymology / Q000502:physiology*; D004357:Drug Synergism; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008387:Marine Toxins; D008564:Membrane Potentials / Q000187:drug effects; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology; D010080:Oxazoles / Q000494:pharmacology; D011689:Purkinje Cells / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D051381:Rats; D011963:Receptors, GABA-A / Q000502:physiology; D015398:Signal Transduction; D019311:Staurosporine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D007093:Imidazoles; D008387:Marine Toxins; D010080:Oxazoles; D011963:Receptors, GABA-A; C031938:calmidazolium; D005680:gamma-Aminobutyric Acid; C063302:KN 62; C059041:calyculin A; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019311:Staurosporine; D002118:Calcium