Abstract
Endothelin (ET)-mediated Ca++ signaling in NG108-15 neuroblastoma x glioma cells was studied by measuring free intracellular Ca++ (Ca++i) levels with the fluorescent Ca++ indicator, fura-2. ET-1 produced biphasic increases in Ca++i consisting of a transient peak elevation followed by a sustained plateau phase. Both peak and plateau Ca++i responses to 5 nM ET-1 were reduced by depletion of extracellular Ca++. Peak responses were also attenuated by inhibitors of inositol phosphate metabolism, whereas plateau responses were affected by dihydropyridine Ca++ channel agonists and antagonists and by differentiation. These results suggest that peak Ca++i responses to ET-1 involve mobilization of Ca++ from inositol phosphate-sensitive intracellular stores and influx of extracellular Ca++ through nonclassical Ca++ channels, whereas plateau responses are mediated by Ca++ influx through dihydropyridine-sensitive, voltage-gated channels.
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|