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Scientific article
English

InsP3 and Ins(1,3,4,5)P4 act in synergy to stimulate influx of extracellular Ca2+ in Xenopus oocytes

Published inThe American journal of physiology, vol. 262, no. 6 Pt 1, p. C1456-1463
Publication date1992
Abstract

To investigate the role of D-myo-inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P4] in the regulation of Ca2+ influx, we injected inositol phosphates into Xenopus oocytes and measured Ca(2+)-gated Cl- current to assay intracellular free Ca2+ concentration ([Ca2+]i). To assess Ca2+ influx, we removed extracellular Ca2+ or added the inorganic Ca2+ channel blocker Mn2+ to the extracellular bath and measured the resulting change in Cl- current. Ins(1,3,4,5)P4 did not cause Ca2+ influx when injected alone or when preceded by an injection of Ca2+. In contrast, Ins(1,3,4,5)P4 stimulated Ca2+ influx when injected after the poorly metabolized inositol trisphosphate (InsP3) analogues D-myo-inositol 1,4,5-trisphosphorothioate [Ins(1,4,5)P3S3] or D-myo-inositol 2,4,5-trisphosphate [Ins(2,4,5)P3]. These results indicate that Ins(1,3,4,5)P4 is not sufficient to stimulate Ca2+ influx but acts in synergy with InsP3s to cause Ca2+ influx. We also studied the effect of Ca2+ influx on the immediate metabolism of D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] in single oocytes. Ca2+ influx shunted the metabolism of Ins(1,4,5)P3 toward the formation of Ins(1,3,4,5)P4 and away from D-myo-inositol 1,4-bisphosphate [Ins(1,4)P2]. These results suggest that there is a positive feedback regulatory mechanism in which Ca2+ influx stimulates Ins(1,3,4,5)P4 production and Ins(1,3,4,5)P4 stimulates further Ca2+ influx.

Keywords
  • Animals
  • Biological Transport/drug effects
  • Calcium/ metabolism
  • Chloride Channels
  • Chromatography, High Pressure Liquid
  • Drug Synergism
  • Female
  • Inositol 1,4,5-Trisphosphate/metabolism/ pharmacology
  • Inositol Phosphates/isolation & purification/metabolism/ pharmacology
  • Ion Channels/physiology
  • Kinetics
  • Manganese/pharmacology
  • Membrane Proteins/drug effects/physiology
  • Oocytes/drug effects/ metabolism
  • Time Factors
  • Xenopus laevis
Citation (ISO format)
DELISLE, S. et al. InsP3 and Ins(1,3,4,5)P4 act in synergy to stimulate influx of extracellular Ca2+ in Xenopus oocytes. In: The American journal of physiology, 1992, vol. 262, n° 6 Pt 1, p. C1456–1463.
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ISSN of the journal0002-9513
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