The lysosomal Ca2+ pool in MDCK cells can be released by ins(1,4,5)P3-dependent hormones or thapsigargin but does not activate store-operated Ca2+ entry

In several cell types, Ca²⁺ release from intracellular Ca²⁺ stores by Ins(1,4,5)P₃ elicits Ca²⁺ influx from the extracellular space into the cytoplasm, termed store-operated Ca²⁺ entry (SOCE). In MDCK cells, the Ins(1,4,5)P₃-sensitive Ca²⁺ store giving rise to SOCE essentially overlaps with the thapsigargin (TG)-sensitive store. Recent evidence suggests that in MDCK cells lysosomes form a Ca²⁺ pool that is functionally coupled with the Ins(1,4,5)P₃-sensitive Ca²⁺ store: Ca²⁺ can be selectively released from lysosomes by glycyl-L-phenylalanine naphthylamide, an agent inducing lysosomal swelling with subsequent and reversible permeabilization of the vesicular membranes. This compartment is also depleted by Ins(1,4,5)P₃-dependent agonists or TG, indicating that it is part of a larger, Ins(1,4,5)P₃-sensitive Ca²⁺ pool. Here we show that whereas SOCE is triggered by Ca²⁺ release from the entire Ins(1,4,5)P₃-sensitive Ca²⁺ pool, selective Ca²⁺ release from lysosomes alone is unable to trigger SOCE. This finding is consistent with measurements of the store-operated cation current, a direct parameter for store-operated Ca²⁺ and Na⁺ entry into MDCK cells. Hence it is proposed that the Ins(1,4,5)P₃-sensitive Ca²⁺ pool is composed of different intracellular compartments that do not uniformly stimulate Ca²⁺ entry into the cell.