Glutamate elicits an outward K+ current which is normally suppressed by a Ca2+/calmodulin-dependent protein kinase II.
The inhibitory action of glutamate (Glu) was examined in identified Euhadra neurons, using the voltage-clamp method in combination with the pressure injection technique. Glu elicited a slow outward K+ current (Glu current) whose amplitude was dose-dependent. This current was inhibited by exogenous Ca2+/calmodulin-dependent protein kinase II (CaMKII) and is enhanced by a specific CaMKII inhibitor. However, no significant changes in the Glu current were observed when the catalytic subunit of protein kinase A (PKA) or the protein kinase C (PKC) fragment (530-558) was intracellularly applied; or using a PKA inhibitor or a PKC inhibitor. Neither the antagonists of the Glu receptor, D-2-amino-5-monophosphonovalerate, 6-cyano-7-nitroquinoxaline-2,3 dione and kynurenic acid, nor the G protein blockers, pertussis toxin and chorela toxin, had any significant effect on the Glu current. These results indicate that Glu opens the CaMKII-suppressing K+ channels, suggesting a novel Glu-induced inhibitory mechanism.
Watanabe
K
K
Department of Physiology, Gifu University School of Medicine, Japan.
Onozuka
M
M
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives; D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002462:Cell Membrane / Q000502:physiology; D002772:Cholera Toxin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D017952:Ganglia, Invertebrate / Q000502:physiology; D018698:Glutamic Acid / Q000494:pharmacology*; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D007736:Kynurenic Acid / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D037342:Pertussis Toxin; D010879:Piperazines / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D047428:Protein Kinase Inhibitors; D012908:Snails; D019311:Staurosporine; D013449:Sulfonamides; D013997:Time Factors; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000470:Alkaloids; D007546:Isoquinolines; D010879:Piperazines; D015221:Potassium Channels; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D010566:Virulence Factors, Bordetella; D018698:Glutamic Acid; C063302:KN 62; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D002772:Cholera Toxin; D037342:Pertussis Toxin; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D007736:Kynurenic Acid; D019311:Staurosporine; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide