Fast kinetics of calcium release induced by myo-inositol trisphosphate in permeabilized rat hepatocytes

J Biol Chem. 1989 Oct 25;264(30):17665-73.

Abstract

We used a stopped-flow method for determining the kinetic properties (between 10 ms and 10 s) of the Ca2+ release induced by inositol 1,4,5-trisphosphate (InsP3) in saponin-treated rat hepatocytes. Preliminary experiments ensured that the indicator was able to monitor rapid changes in free Ca2+ reliably. At 20 degrees C, a maximally efficient concentration of 10 microM InsP3 released Ca2+ with a half-time of 150-300 ms, the initial rate being about 1-2 nmol of Ca2+/mg of cell protein/s. The delay between the addition of 10 microM InsP3 and the onset of Ca2+ release was shorter than 20 ms, suggesting that the opening process of Ca2+ channels after binding of InsP3 to receptors is completed within a few milliseconds. Half-maximal initial rates for Ca2+ release occurred at about 1 microM InsP3 (Hill index was 1.6). The resulting Ca2+ efflux had a moderate temperature dependence. It could not be fitted to a single exponential. After low speed centrifugation of saponin-treated cells (1000 x g for 1 min), part of the InsP3-sensitive Ca2+ pool was recovered in the cell-free supernatant fraction, suggesting that the response to InsP3 arises from a vesicular fraction which may diffuse from the saponin-treated cells into the medium.

MeSH terms

  • Aminoquinolines
  • Animals
  • Calcium / metabolism*
  • Cell Membrane Permeability
  • Cells, Cultured
  • Female
  • Fluorescent Dyes
  • Inositol 1,4,5-Trisphosphate / pharmacology*
  • Kinetics
  • Liver / drug effects
  • Liver / metabolism*
  • Rats
  • Rats, Inbred Strains
  • Saponins
  • Spectrometry, Fluorescence
  • Thermodynamics

Substances

  • Aminoquinolines
  • Fluorescent Dyes
  • Saponins
  • Inositol 1,4,5-Trisphosphate
  • Quin2
  • Calcium