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Role of STIM1 in Regulation of Store‐Operated Ca 2+ Entry in PC12 cells
Author(s) -
Prakash Y S,
Pabelick Christina M,
Thompson Michael A
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1181.1
Subject(s) - stim1 , cyclopiazonic acid , extracellular , chemistry , endoplasmic reticulum , stimulation , glutamate receptor , intracellular , microbiology and biotechnology , endocrinology , medicine , biochemistry , biology , receptor
Store operated calcium entry (SOCE) is important for regulation of intracellular Ca 2+ ([Ca 2+ ] i ) in neurons. Recent studies in other cell type suggest that stromal interaction molecule (STIM1) triggers SOCE. We examined the role of STIM1 in the sensitivity of SOCE to temperature, pH and glutamate in differentiated, fura‐2 loaded rat pheochromocytoma (PC12) cells, a model for neuronal cells. In STIM1 siRNA‐transfected vs. control cells, SOCE was triggered by introduction of extracellular Ca 2+ following endoplasmic reticulum depletion via cyclopiazonic acid in zero Ca 2+ . Cells were washed and exposed to altered pH (6.0–8.0), altered temperature (34–40 o C) or different concentrations of glutamate. In controls, SOCE was progressively inhibited by decreased pH or temperature, while alkalosis and increased temperature stimulated Ca 2+ influx. Increasing glutamate concentrations progressively inhibited SOCE. siRNA inhibition of STIM1 substantially blunted both temperature sensitivity (especially increased temperature) and pH sensitivity (especially acidic pH) of SOCE. These data show that SOCE in PC12 cells is susceptible to acidosis, temperature, and agonist stimulation: factors that can adversely affect neuronal function under pathological conditions. In this regard, the SOCE triggering protein STIM1 may play a role in such susceptibility. This work has been supported by NIH grants UL1RR024150‐01(CR to CMP, CR20 and Early Career Development Award to YSP), and the Department of Anesthesiology (CMP, YSP), Mayo Clinic College of Medicine, Rochester, MN