Calcium-sensing receptor activation induces intracellular calcium oscillations

Gerda E. Breitwieser, Lucio Gama

Research output: Contribution to journalArticlepeer-review

Abstract

Parathyroid hormone secretion is exquisitely sensitive to small changes in serum Ca2+ concentration, and these responses are transduced via the Ca2+-sensing receptor (CaR). We utilized heterologous expression in HEK-293 cells to determine the effects of small, physiologically relevant perturbations in extracellular Ca2+ on CaR signaling via phosphatidylinositol-phospholipase C, using changes in fura 2 fluorescence to quantify intracellular Ca2+. Chronic exposure of CaR-transfected cells to Ca2+ in the range from 0.5 to 3 mM modulated the resting intracellular Ca2+ concentration and the subsequent cellular responses to acute extracellular Ca2+ perturbations but had no effect on thapsigargin-sensitive Ca2+ stores. Modest, physiologically relevant increases in extracellular Ca2+ concentration (0.5 mM increments) caused sustained (30-40 min) low-frequency oscillations of intracellular Ca2+ (∼45 s peak to peak interval). Oscillations were eliminated by 1 μM thapsigargin but were insensitive to protein kinase inhibitors (staurosporine, KN-93, or bisindolylmaleimide I). Staurosporine did increase the fraction of cells oscillating at a given extracellular Ca2+ concentration. Serum Ca2+ concentrations thus chronically regulate cells expressing CaR, and small perturbations in extracellular Ca2+ alter both resting intracellular Ca2+ as well as Ca2+ dynamics.

Original languageEnglish (US)
Pages (from-to)C1412-C1421
JournalAmerican Journal of Physiology - Cell Physiology
Volume280
Issue number6 49-6
DOIs
StatePublished - 2001

Keywords

  • Calcium oscillations
  • Fura 2
  • HEK-293 cells
  • Intracellular calcium
  • Protein kinase inhibitors
  • Thapsigargin-sensitive calcium stores

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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