KINETICS OF THE NONSPECIFIC CALCIUM LEAK FROM NONMITOCHONDRIAL CALCIUM STORES IN PERMEABILIZED A7R5 CELLS

We have investigated the detailed kinetics of the passive Ca2+ leak fr om non-mitochondrial Ca2+ stores in permeabilized A7r5 cells. The decr ease in the content of stored Ca2+ in the presence of 2 mu M thapsigar gin deviated from a single-exponential curve in the initial phase of t he efflux. The deviation persisted after correcting this efflux for pa ssively bound Ca2+. The non-single-exponential nature of the spontaneo us release also occurred when the initial store Ca2+ content was reduc ed to 40% of its original value by pretreatment with 200 nM inositol 1 ,4,5-trisphosphate (InsP(3)). The passive Ca2+ leak could be modelled by two exponential curves with discrete rate constants of 0.06 min(-1) and 0.98 min(-1), and not by any other type of nonexponential decay. We concluded that individual store units are heterogeneous with respec t to their passive Ca2+ permeability. This non-exponential nature of t he passive Ca2+ release is unrelated to the non-single-exponential Ins P(3)-induced Ca2+ release.