Epidermal Growth Factor Activates Store-operated Ca2+ Channels through an Inositol 1,4,5-Trisphosphate-independent Pathway in Human Glomerular Mesangial Cells

Wei Ping Li, Leonidas Tsiokas, Steven C. Sansom, Rong Ma

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

One of the fastest cellular responses following activation of epidermal growth factor receptor is an increase in intracellular Ca2+ concentration. This event is attributed to a transient Ca2+ release from internal stores and Ca2+ entry from extracellular compartment. Store-operated Ca2+ channels are defined the channels activated in response to store depletion. In the present study, we determined whether epidermal growth factor activated store-operated Ca2+ channels and further, whether depletion of internal Ca2+ stores was required for the epidermal growth factor-induced Ca2+ entry in human glomerular mesangial cells. We found that 100 nM epidermal growth factor activated a Ca2+-permeable channel that had identical biophysical and pharmacological properties to channels activated by 1 μM thapsigargin in human glomerular mesangial cells or A431 cells. The epidermal growth factor-induced Ca2+ currents were completely abolished by a selective phospholipase C inhibitor, U73122. However, xestospongin C, a specific inositol 1,4,5-trisphosphate receptor inhibitor, did not affect the membrane currents elicited by epidermal growth factor despite a slight reduction in background currents. Following emptying of internal Ca 2+ stores by thapsigargin, epidermal growth factor still potentiated the Ca2+ currents as determined by the whole-cell patch configuration. Furthermore, epidermal growth factor failed to trigger measurable Ca2+ release from endoplasmic reticulum. However, another physiological agent linked to phospholipase C and inositol 1,4,5-trisphosphate cascade, angiotensin II, produced a striking Ca2+ transient. These results indicate that epidermal growth factor activates store-operated Ca 2+ channels through an inositol 1,4,5-trisphosphate-independent, but phospholipase C-dependent, pathway in human glomerular mesangial cells.

Original languageEnglish (US)
Pages (from-to)4570-4577
Number of pages8
JournalJournal of Biological Chemistry
Volume279
Issue number6
DOIs
StatePublished - Feb 6 2004

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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