A xestospongin C-sensitive Ca2+ store is required for cAMP-induced Ca2+ influx and cAMP oscillations in Dictyostelium

Xestospongin C (XeC) is known to bind to the inositol 1,4,5-trisphosphate (IP3)-sensitive store in mammalian cells and to inhibit IP3- and thapsigargin-induced Ca2+ release. In this study we show that this is also true for Dictyostelium, In addition, XeC inhibited Ca2+ uptake into purified vesicle fractions and induced Ca2+ release. This suggests that, in the case of Dictyostelium, XeC opens rather than plugs the LP, receptor channel as was proposed for mammalian cells (Gafni, J., Munsch, J. A., Lam, T. H., Catlin, RI. C., Costa, L. G., Molinski, T, F., and Pessah, I. N. (1997) Neuron 19, 725-733), In order to elucidate the function of the XeC-sensitive Ca2+ store in Dictyostelium during differentiation, we applied XeC to the cells and found that it caused a time-dependent increase of basal [Ca2+](i) and inhibited cAMP-induced Ca2+ influx in single cells as well as in cell suspensions. Moreover, XeC blocked light scattering spikes and pulsatile cAMP signaling.