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

Xibao Liu, Hwei Ling Ong, Biswaranjan Pani, Katherine Johnson, William B. Swaim, Brij Singh, Indu Ambudkar

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

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 1μM Gd3+-sensitive, inwardly rectifying, cation current, ISOC, while hypotonic solution (150mOsm) induced cell swelling and activated an outwardly rectifying cation current that was blocked by 100μM Gd3+ but not by 2APB. HTS addition before or after Tg attenuated the sensitivity of Ca2+ influx to 2APB and 1μM Gd3+. After HTS-induced volume increase, while stimulation of cells with Tg resulted in intracellular Ca2+ release without Ca2+ influx, stimulation with CCh caused neither internal Ca2+ release nor Ca2+ 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.

Original languageEnglish (US)
Pages (from-to)491-499
Number of pages9
JournalCell Calcium
Volume47
Issue number6
DOIs
StatePublished - Jun 2010
Externally publishedYes

Keywords

  • Cell volume
  • ER-PM junctional domains
  • Hypotonic stress
  • Orai1
  • SOCE
  • STIM1
  • TRPC1

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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