RELATIONSHIP BETWEEN INTRACELLULAR CALCIUM STORE DEPLETION AND CALCIUM RELEASE-ACTIVATED CALCIUM CURRENT IN A MAST-CELL LINE (RBL-1)

The kinetic relationship between depletion of endoplasmic reticulum ca lcium stores and the activation of a calcium release-activated calcium current (I-crac) was investigated in the RBL-1 mast cell line. The in ositol trisphosphate receptor activator, inositol 2,4,5-trisphosphate ((2,4,5)IP3), the sarcoplasmic-endoplasmic reticulum calcium ATPase in hibitor, thapsigargin, and the calcium ionophore, ionomycin, were used to deplete stored calcium. For (2,4,5)IP3 and thapsigargin, a signifi cant delay was observed between the initiation of calcium store deplet ion and the activation of I-crac. However, for ionomycin, little or no delay was observed. This may indicate that a specialized subcompartme nt of the endoplasmic reticulum functions as a regulator of calcium en try and that this compartment is relatively resistant to depletion by (2,4,5)IP3 and thapsigargin but not to depletion by ionomycin. For all three calcium-depleting agents, the rate of development of I-crac. on ce initiated, was relatively constant, suggesting an all-or-none mecha nism. However, there were also clear experimental situations in which submaximal, graded depletion of stored calcium resulted in submaximal activation of I-crac. This complex behavior could also result from the existence of a specific subcompartment of endoplasmic reticulum regul ating I-crac. The kinetic behavior of this compartment may not be accu rately reflected by the kinetics of calcium changes in the bulk of end oplasmic reticulum. These findings add to the growing body of evidence suggesting specialization of the endoplasmic reticulum calcium stores with regard to the control of capacitative calcium entry.