Kinetics of the non-specific calcium leak from non-mitochondrial calcium stores in permeabilized A7r5 cells

We have investigated the detailed kinetics of the passive Ca2+ leak from non-mitochondrial Ca2+ stores in permeabilized A7r5 cells. The decrease in the content of stored Ca2+ in the presence of 2 mu M thapsigargin deviated from a single-exponential curve in the initial phase of the efflux. The deviation persisted after correcting this efflux for passively bound Ca2+. The non-single-exponential nature of the spontaneous release also occurred when the initial store Ca2+ content was reduced 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 respect to their passive Ca2+ permeability. This non-exponential nature of the passive Ca2+ release is unrelated to the non-single-exponential InsP(3)-induced Ca2+ release.