TRPC1 functions as a store-operated Ca2+ channel in intestinal epithelial cells and regulates early mucosal restitution after wounding

Jaladanki N. Rao, Oleksandr Platoshyn, Vera A. Golovina, Lan Liu, Tongtong Zou, Bernard S. Marasa, Douglas J. Turner, Jason Yuan, Jian Ying Wang

Research output: Contribution to journalArticle

90 Citations (Scopus)

Abstract

An increase in cytosolic free Ca2+ concentration ([Ca 2+]cyt) results from Ca2+ release from intracellular stores and extracellular Ca2+ influx through Ca 2+-permeable ion channels and is crucial for initiating intestinal epithelial restitution to reseal superficial wounds after mucosal injury. Capacitative Ca2+ entry (CCE) induced by Ca2+ store depletion represents a major Ca2+ influx mechanism, but the exact molecular components constituting this process remain elusive. This study determined whether canonical transient receptor potential (TRPC)1 served as a candidate protein for Ca2+-permeable channels mediating CCE in intestinal epithelial cells and played an important role in early epithelial restitution. Normal intestinal epithelial cells (the IEC-6 cell line) expressed TRPC1 and TPRC5 and displayed typical records of whole cell store-operated Ca2+ currents and CCE generated by Ca2+ influx after depletion of intracellular stores. Induced TRPC1 expression by stable transfection with the TRPC1 gene increased CCE and enhanced cell migration during restitution. Differentiated IEC-Cdx2L1 cells induced by forced expression of the Cdx2 gene highly expressed endogenous TRPC1 and TRPC5 and exhibited increased CCE and cell migration. Inhibition of TRPC1 expression by small interfering RNA specially targeting TRPC1 not only reduced CCE but also inhibited cell migration after wounding. These findings strongly suggest that TRPC1 functions as store-operated Ca2+ channels and plays a critical role in intestinal epithelial restitution by regulating CCE and intracellular [Ca2+]cyt.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume290
Issue number4
DOIs
StatePublished - Apr 2006
Externally publishedYes

Fingerprint

Cell Movement
Epithelial Cells
Wounds and Injuries
Ion Channels
Small Interfering RNA
Transfection
Gene Expression
Cell Line
Genes
Proteins

Keywords

  • Ca influx
  • Canonical transient receptor potential 1
  • Intracellular Ca
  • Mucosal injury
  • Polyamines
  • Rapid mucosal repair
  • Voltage-gated K channels

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology

Cite this

TRPC1 functions as a store-operated Ca2+ channel in intestinal epithelial cells and regulates early mucosal restitution after wounding. / Rao, Jaladanki N.; Platoshyn, Oleksandr; Golovina, Vera A.; Liu, Lan; Zou, Tongtong; Marasa, Bernard S.; Turner, Douglas J.; Yuan, Jason; Wang, Jian Ying.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 290, No. 4, 04.2006.

Research output: Contribution to journalArticle

Rao, Jaladanki N. ; Platoshyn, Oleksandr ; Golovina, Vera A. ; Liu, Lan ; Zou, Tongtong ; Marasa, Bernard S. ; Turner, Douglas J. ; Yuan, Jason ; Wang, Jian Ying. / TRPC1 functions as a store-operated Ca2+ channel in intestinal epithelial cells and regulates early mucosal restitution after wounding. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 2006 ; Vol. 290, No. 4.
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