TY - JOUR
T1 - InsP3 and Ins(1,3,4,5)P4 act in synergy to stimulate influx of extracellular Ca2+ in Xenopus oocytes
AU - DeLisle, S.
AU - Pittet, D.
AU - Potter, B. V.L.
AU - Lew, P. D.
AU - Welsh, M. J.
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 1992
Y1 - 1992
N2 - 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 Ca2+-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.
AB - 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 Ca2+-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.
KW - D-myo-inositol 1,3,4,5- tetrakisphosphate
KW - extracellular calcium influx
KW - inositol trisphosphate
KW - intracellular calcium concentration
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U2 - 10.1152/ajpcell.1992.262.6.c1456
DO - 10.1152/ajpcell.1992.262.6.c1456
M3 - Article
C2 - 1377444
AN - SCOPUS:0026633525
VL - 262
SP - C1456-C1463
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
SN - 0363-6135
IS - 6 31-6
ER -