Multistep mechanism of polarized Ca2+ wave patterns in hepatocytes

M. H. Nathanson, A. D. Burgstahler, M. B. Fallon

Research output: Contribution to journalArticlepeer-review

66 Scopus citations


The spatial organization of cytosolic Ca2+ (Ca(i)/2+) signals is thought to be important for regulation of cell function. In epithelial cells, the involvement of inositol 1,4,5,-trisphosphate (IP3)-mediated Ca2+ release in evoking Ca(i)2+ signals is appreciated, but the location of IP3-sensitive Ca2+ stores and the role of Ca2+-induced Ca2+ release (CICR) for Ca2+ signaling are less defined. Here, we demonstrate that IP3 receptors are localized to the apical region in hepatocytes. We also show that hormone-induced Ca(i)2+ waves propagate across the cell at a rate that depends on mobilization of Ca2+ stores that are sensitive to caffeine, ryanodine, and dantrolene, and that these agents, at concentrations that inhibit CICR, decrease the magnitude of Ca(i)2+ signals. Furthermore, Ca(i)2+ wave speed is not reduced in Ca2+-free medium. These findings suggest that Ca(i)2+ signals in epithelial cells begin as apical-to-basal Ca(i)2+ waves that result from sequential release of Ca2+, first from IP3-sensitive stores in the apex and then from Ca2+-sensitive stores distributed across the remainder of the cell.

Original languageEnglish (US)
Pages (from-to)G338-G349
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Issue number3 30-3
StatePublished - 1994


  • caffeine
  • calcium- induced calcium release
  • confocal microscopy
  • dantrolene
  • inositol 1,4,5-trisphosphate
  • ryanodine

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)


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