Regulation of PDGF-β receptor-operated Ca2+ channels by phospholipase C-γ1 in glomerular mesangial cells

M. A. Heping, Hiroshi Matsunaga, L. I. Bing, Mark B. Marrero, Brian N. Ling

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Platelet-derived growth factor (PDGF)-induced Ca2+ signaling mechanisms were examined in cultured rat glomerular mesangial cells. PDGF-BB stimulated the tyrosine phosphorylation of phospholipase C (PLC)-γ1, the formation of a PLC-γ1/PDGF-β receptor membrane complex, and the generation of intracellular inositol 1,4,5-trisphosphate (IP3). Preincubation with a tyrosine kinase inhibitor (genistein) abolished these PDGF-induced responses. Activation of 1-pS Ca2+ channels in cell-attached patches by intrapipette PDGF-BB was also abolished by tyrosine kinase inhibition. In the absence of PDGF-BB, channels were activated in cell-attached patches exposed to intrapipette thapsigargin (IP3-independent releaser of intracellular Ca2+ stores) and in excised inside-out patches exposed to increasing 'cytoplasmic' Ca2+ (10-8 to 10-6 M). In cell-attached patches, channel activation by PDGF-BB was abolished when extracellular Ca2+ was <1 mM. In glomerular mesangial cells 1) PDGF-BB stimulates tyrosine phosphorylation of PLC-γ1, PDGF-β receptor/PLC-γ1 membrane complex formation, IP3 production, and 1- pS Ca2+ channel activity; 2) all four PDGF-induced responses are abolished by tyrosine kinase inhibition; 3) PDGF receptor-operated Ca2+ channels are sensitive to both intra- and extracellular Ca2+.

Original languageEnglish (US)
Pages (from-to)F994-F1003
JournalAmerican Journal of Physiology
Volume271
Issue number5 PART 2
StatePublished - Dec 16 1996

Keywords

  • calcium signaling
  • D-myo- inositol 1,4,5-trisphosphate
  • phosphorylation
  • platelet-derived growth factor
  • tyrosine kinase

ASJC Scopus subject areas

  • Physiology (medical)

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    Heping, M. A., Matsunaga, H., Bing, L. I., Marrero, M. B., & Ling, B. N. (1996). Regulation of PDGF-β receptor-operated Ca2+ channels by phospholipase C-γ1 in glomerular mesangial cells. American Journal of Physiology, 271(5 PART 2), F994-F1003.