Inhibition of high voltage-activated calcium currents by L-glutamate receptor-mediated calcium influx.
The modulation of high voltage-activated (HVA) Ca2+ currents by L-glutamate and its agonists was investigated in cultured rat hypothalamic neurons. L-Glutamate and agonists selective for NMDA or non-NMDA receptors reversibly inhibited HVA Ca2+ currents. The putative presynaptic glutamate receptor agonist L-2-amino-4-phosphonobutyric acid and the selective metabotropic agonist trans-ACPD were ineffective. Inhibition was dependent on the presence of extracellular Ca2+ and blocked by internal perfusion of the cells with BAPTA. The calmodulin antagonists trifluoperazine and calmidazolium completely prevented the inhibition. Increases in the intracellular Ca2+ concentration due to Ca2+ influx through non-NMDA receptor channels were visualized using fura-2. These results indicate that not only NMDA but also non-NMDA receptor channels in these neurons are permeable for Ca2+ and that Ca2+ influx through these channels activates a calmodulin-dependent mechanism, which leads to HVA Ca2+ current inhibition.
Zeilhofer
H U
HU
Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Universität Erlangen-Nürnberg, Germany.
Müller
T H
TH
Swandulla
D
D
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects*; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004553:Electric Conductivity; D005260:Female; D005971:Glutamates / Q000494:pharmacology*; D018698:Glutamic Acid; D007031:Hypothalamus / Q000502:physiology; D007093:Imidazoles / Q000494:pharmacology; D009474:Neurons / Q000502:physiology; D011810:Quinoxalines / Q000494:pharmacology; D016318:Quisqualic Acid / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology; D014268:Trifluoperazine / Q000494:pharmacology
D015220:Calcium Channels; D005971:Glutamates; D007093:Imidazoles; D011810:Quinoxalines; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D014268:Trifluoperazine; D018698:Glutamic Acid; C031938:calmidazolium; D004533:Egtazic Acid; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D016318:Quisqualic Acid; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium