Na(+) channel regulation by calmodulin kinase II in rat cerebellar granule cells.
The effects of specific CaM kinase II inhibitors were investigated on Na(+) channels from rat cerebellar granule cells. A maximal effect of KN-62 was observed at 20 microM and consisted of an 80% reduction of the peak Na(+) current after only a 10-min application. A hyperpolarizing shift of 8 mV in the steady-state inactivation was also observed. KN-04 (20 microM), an inactive analog, had no detectable effect. KN-62 was however inactive on Na(+) currents recorded from Chinese hamster ovary cells expressing the type II A alpha subunit. We have also analyzed the inhibitory effects of CaM kinase II 296-311 and CaM kinase II 281-309 peptides. Both peptides (75 microM) induced a maximum peak Na(+) current reduction within 30 min. Under similar conditions, a truncated peptide CaM kinase II 284-302 was ineffective. These results demonstrate that CaM kinase II acts as a modulator of Na(+) channel activity in cerebellar granule cells.
Institut National de la Santé et de la Recherche Médicale U464, Laboratoire de Neurobiologie des Canaux Ioniques, Faculté de Médecine Secteur Nord, Institut Jean Roche, Marseille Cedex 20, 13916, France. carlier.e@jean-roche.univ-mrs.fr
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Carlier
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Dargent
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De Waard
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Couraud
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D016466:CHO Cells; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017136:Ion Transport / Q000187:drug effects; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*
D004791:Enzyme Inhibitors; D010446:Peptide Fragments; D015222:Sodium Channels; C065344:KN 04; C063302:KN 62; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D012964:Sodium; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases