Depletion of intracellular calcium stores activates a calcium current in mast cells

Nature. 1992 Jan 23;355(6358):353-6. doi: 10.1038/355353a0.


In many cell types, receptor-mediated Ca2+ release from internal stores is followed by Ca2+ influx across the plasma membrane. The sustained entry of Ca2+ is thought to result partly from the depletion of intracellular Ca2+ pools. Most investigations have characterized Ca2+ influx indirectly by measuring Ca(2+)-activated currents or using Fura-2 quenching by Mn2+, which in some cells enters the cells by the same influx pathway. But only a few studies have investigated this Ca2+ entry pathway more directly. We have combined patch-clamp and Fura-2 measurements to monitor membrane currents in mast cells under conditions where intracellular Ca2+ stores were emptied by either inositol 1,4,5-trisphosphate, ionomycin, or excess of the Ca2+ chelator EGTA. The depletion of Ca2+ pools by these independent mechanisms commonly induced activation of a sustained calcium inward current that was highly selective for Ca2+ ions over Ba2+, Sr2+ and Mn2+. This Ca2+ current, which we term ICRAC (calcium release-activated calcium), is not voltage-activated and shows a characteristic inward rectification. It may be the mechanism by which electrically nonexcitable cells maintain raised intracellular Ca2+ concentrations and replenish their empty Ca2+ stores after receptor stimulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels / drug effects
  • Calcium Channels / physiology*
  • Cations, Divalent
  • Cell Membrane Permeability / drug effects
  • Cells, Cultured
  • Egtazic Acid / analogs & derivatives
  • Egtazic Acid / pharmacology
  • Inositol 1,4,5-Trisphosphate / pharmacology*
  • Ionomycin / pharmacology
  • Mast Cells / drug effects
  • Mast Cells / physiology*
  • Membrane Potentials / drug effects
  • Rats
  • Terpenes / pharmacology
  • Thapsigargin


  • Calcium Channel Blockers
  • Calcium Channels
  • Cations, Divalent
  • Terpenes
  • Egtazic Acid
  • Ionomycin
  • Thapsigargin
  • Inositol 1,4,5-Trisphosphate
  • 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
  • Calcium