Cell Calcium. 2010 Jun;47(6):491-9. doi: 10.1016/j.ceca.2010.04.002. Epub 2010 May 20.

Effect of cell swelling on ER/PM junctional interactions and channel assembly involved in SOCE.External 2231691f894ba696de1310221b0a0dbbb31a7251e75115c265587c3d9d5f507c

Liu, X., Ong, H. L., Pani, B., Johnson, K., Swaim, W. B., Singh, B., Ambudkar, I.,
["Secretory Physiology Section, Molecular Physiology and Therapeutics Branch, National Institutes of Dental and Craniofacial Research, Bethesda, MD 20892, USA."]
Store-operated calcium entry (SOCE) regulates critical cellular functions and is determined by precise ER/plasma membrane (PM) junctional interactions. Here we have assessed the effect of hypotonic cell volume increase on SOCE in a salivary gland epithelial cell line (HSG). Thapsigargin (Tg) activated a 2APB- and 1microM Gd(3+)-sensitive, inwardly rectifying, cation current, I(SOC), while hypotonic solution (150mOsm) induced cell swelling and activated an outwardly rectifying cation current that was blocked by 100microM Gd(3+) but not by 2APB. HTS addition before or after Tg attenuated the sensitivity of Ca(2+) influx to 2APB and 1microM Gd(3+). After HTS-induced volume increase, while stimulation of cells with Tg resulted in intracellular Ca(2+) release without Ca(2+) influx, stimulation with CCh caused neither internal Ca(2+) release nor Ca(2+) influx. Importantly, HTS caused the ER to recede from the plasma membrane which prevented Tg-stimulated clustering of STIM1 in the ER/PM region and association of STIM1 with TRPC1 and Orai1. Disruption of SOCE was dependent on the level of hypotonic stress as 225mOsm HTS induced relatively less cell swelling or disruption of SOCE. These results demonstrate that epithelial cells can tolerate small increases (up to 5%) in cell volume while larger increases lead to disruption of ER-PM interactions that are critical for activation of SOCE. We suggest that loss of SOCE could impact cell function and contribute to the deleterious effects of severe hypotonic stress.
PMID: 20488539External 2231691f894ba696de1310221b0a0dbbb31a7251e75115c265587c3d9d5f507c
Validation: In vivo validation Toggle 893349bafcc528f8346c51dc3420151d67b0126b2c122dd1017121c03fa0f69b
  Assay with endogenous proteins Assay with overexpressed proteins Reference
Cell or tissue Cell or tissue TRP channel construct Interactor construct
TRP channel Interactor Method Species Region Species Region
TRPC1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 STIM1 Co-immunoprecipitation HSG cell 20488539
(Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
TRP / Interactor

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