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-glut amate and its agonists was investigated in cultured rat hypothalamic n eurons. L-Glutamate and agonists selective for NMDA or non-NMDA recept ors reversibly inhibited HVA Ca2+ currents. The putative presynaptic g lutamate receptor agonist L-2-amino-4-phosphonobutyric acid and the se lective metabotropic agonist trans-ACPD were ineffective. Inhibition w as dependent on the presence of extracellular Ca2+ and blocked by inte rnal perfusion of the cells with BAPTA. The calmodulin antagonists tri fluoperazine and calmidazolium completely prevented the inhibition. In creases in the intracellular Ca2+ concentration due to Ca2+ influx thr ough non-NMDA receptor channels were visualized using fura-2. These re sults indicate that not only NMDA but also non-NMDA receptor channels in these neurons are permeable for Ca2+ and that Ca2+ influx through t hese channels activates a calmodulin-dependent mechanism, which leads to HVA Ca2+ current inhibition.