MODULATION OF AMPA KAINATE RECEPTORS BY CYCLOTHIAZIDE INCREASES CYTOPLASMIC FREE CA2+ AND CA-45(2+) UPTAKE IN BRAIN NEURONS/

alpha-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-induc ed Ca2+ responses, and their modulation by cyclothiazide, were investi gated in two functional assays of Ca2+ channel activity. AMPA produced a marked increase in cytoplasmic free Ca2+ levels ([Ca2+](i)) in sing le cortical neurons, whereas no such effects of AMPA could be observed in intact cerebellar granule neurons. In monolayer cultures of cortic al cells, cyclothiazide caused a pronounced enhancement of AMPA-induce d stimulation of Ca-45(2+) uptake, whereas similar studies in cerebell ar granule neurons revealed only a weak potentiation of AMPA-induced C a-45(2+) uptake. Higher concentrations of cyclothiazide alone produced [Ca2+](i) oscillations as well as an increase of basal Ca-45(2+) upta ke in cortical neurons, whereas no such effects were obtained in cereb ellar granule neurons. Our data indicate that AMPA receptors located o n cortical and cerebellar granule neurons, respectively, may differ in their permeability to Ca2+ and that this difference is markedly poten tiated following the application of cyclothiazide.