INVOLVEMENT OF CA2-INDUCED CA2+ RELEASE IN THE BIPHASIC CA2+ RESPONSEEVOKED BY READDITION OF CA2+ TO THE MEDIUM AFTER UTP-INDUCED STORE DEPLETION IN A431 CELLS()

We have recently shown that the Ca2+ response in endothelial cells evo ked by readdition of Ca2+ to the medium after store depletion caused b y a submaximal concentration of agonist can involve Ca2+ release from Ca2+ stores sensitive to both inositol 1,4,5-trisphosphate and ryanodi ne. The present experiments were performed to determine whether this m echanism might also exist in other types of cell. For this purpose, we used the human carcinoma cell line A431, which has a varied resting [ Ca2+](i). We found that the amplitude of the Ca2+ response evoked by C a2+ readdition did not correlate with the amplitude of the preceding U TP-evoked Ca2+ release, but did positively correlate with the initial [Ca2+](i). An inspection of the two patterns of response seen in this study (the large biphasic and small plateau-shaped Ca2+ responses) rev ealed that there is an accelerating rise in [Ca2+](i) during the bipha sic response. Application of ryanodine during the plateau-shaped Ca2response reversibly transformed it into the biphasic type. Unlike ryan odine, caffeine did not itself evoke Ca2+ release, but it caused a fur ther [Ca2+](i) rise when [Ca2+](i) had already been elevated by thapsi gargin. These data suggest that in A431 cells, as in endothelial cells , the readdition of Ca2+ after agonist-evoked store depletion can evok e Ca2+-induced Ca2+ release. This indicates that Ca2+ entry may be ove restimated by this widely used protocol.