The store-operated calcium current I(CRAC): nonlinear activation by InsP3 and dissociation from calcium release.
Patch-clamp experiments aimed at determining the relationship between intracellular Ca2+ release and activation of store-operated calcium current I(CRAC) reveal that both agonist and InsP3-mediated activation of I(CRAC) are highly nonlinear, occurring over a narrow concentration range. Ca2+ release and Ca2+ influx can be dissociated, as they possess differential sensitivities to InsP3: low concentrations induce substantial Ca2+ release without any activation of I(CRAC), whereas micromolar concentrations of InsP3 are required to activate Ca2+ influx. This suggests functionally distinct stores controlling Ca2+ release and influx and enables cells to switch between sources of Ca2+ to fit best their current needs.
Parekh
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AB
Max-Planck-Institute for Biophysical Chemistry, Göttingen, Germany.
Fleig
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A
Penner
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R
D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D015640:Ion Channel Gating / Q000502:physiology*; D015471:Leukemia, Basophilic, Acute; D017711:Nonlinear Dynamics; D018408:Patch-Clamp Techniques; D051381:Rats; D019284:Thapsigargin / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000502:physiology
D015220:Calcium Channels; D004791:Enzyme Inhibitors; D019284:Thapsigargin; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium