Nitric oxide (NO) may participate in cell–cell communication in the brain by generating intercellular Ca2+ waves. In hippocampal organotypic and dissociated glial–neuron (>80% glia) cultures local applications of aqueous NO induced slowly propagating intercellular Ca2+ waves. In glial cultures, Ca2+ waves and Mn2+ quench of cytosolic fura-2 fluorescence mediated by NO were inhibited by nicardipine, indicating that NO induces Ca2+ influx in glia which is dihydropyridine-sensitive. As NO treatments also depolarised the plasma membrane potential of glia, the nicardipine-sensitive Ca2+ influx might be due to the activation of dihydropyridine-sensitive L-type Ca2+ channels. Both nicardipine-sensitive intercellular Ca2+ waves and propagating cell depolarisation induced by mechanical stress of individual glia were inhibited by pretreating cultures with either an NO scavenger or N G-methyl-L-arginine. Results demonstrate that NO can induce Ca2+ waves in hippocampal slice cultures, and that Ca2+ influx coupled to NO-mediated membrane depolarisation might assist in fashioning their spatio-temporal dynamics.
