AJP - Cell Physiology, Vol 262, Issue 6 C1456-C1463, Copyright © 1992 by American Physiological Society
InsP3 and Ins(1,3,4,5)P4 act in synergy to stimulate influx of extracellular Ca2+ in Xenopus oocytes
S. DeLisle, D. Pittet, B. V. Potter, P. D. Lew and M. J. Welsh
Howard Hughes Medical Institute, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242.
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.
