Cytosolic Ca2+ controls the loading dependence of IP3-induced Ca2+ release

It is still debated whether inositol 1,4,5-trisphosphate(IP3)-induced Ca2+ release is loading-dependent. We now report that stimulation of the IF, receptor by luminal Ca2+ depends on the cytosolic [Ca2+] in permeabilized A7r5 cells. The EC50 and maximal extent of Ca2+ release were loading-dependent in the presence of 5 mM 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid: the EC50 increased 1.9-fold and the maximal release decreased from 88 to 52% when the stores contained 73% less Ca2+. In the presence of 0.3 mu M free Ca2+, the EC50 for filled and less filled stores differed, however, only 1.2-fold and the maximal Ca2+ release was respectively 96 and 87% of the total releasable Ca2+. At 1 mu M free Ca2+, the difference in EC50 between filled and less filled stores again became larger (2.2-fold) and the maximal Ca2+ release decreased from 93 to 87% when the stores contained less Ca2+. (C) 1999 Academic Press.