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.
Haller
T
T
Department of Physiology, University of Innsbruck, Austria.
Völkl
H
H
Deetjen
P
P
Dietl
P
P
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D004151:Dipeptides / Q000494:pharmacology; D004285:Dogs; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D007425:Intracellular Membranes / Q000187:drug effects / Q000502:physiology; D007668:Kidney; D007700:Kinetics; D008247:Lysosomes / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials; D012964:Sodium / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology*
D004151:Dipeptides; C041865:glycylphenylalanine 2-naphthylamide; D019284:Thapsigargin; D015544:Inositol 1,4,5-Trisphosphate; D012964:Sodium; D002118:Calcium