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PMID: 2784673 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The effect of external calcium and pH on inositol trisphosphate-mediated calcium release from cerebellum microsomal fractions.

The Biochemical journal ·Vol. 258 ·No. 1 ·1989-02-15 ·Pages 261-5

Joseph SK, Rice HL, Williamson JR

Abstract

Binding of D-myo-inositol 1,4,5-trisphosphate (InsP3) to rat cerebellum membranes has previously been shown to be stimulated by alkaline pH and inhibited by low concentrations of Ca2+ [Worley, Baraban, Suppatopone, Wilson & Snyder (1987) J. Biol. Chem. 262, 12132-12136]. In the present study, Scatchard analysis of InsP3 binding to cerebellum microsomes indicates that the effects of Ca2+ and pH are exerted through changes in the apparent affinity of the receptor without effects on maximal binding. The influence of extravesicular Ca2+ and pH on InsP3-mediated 45Ca2+ release was investigated. Extravesicular Ca2+ inhibited InsP3-mediated Ca2+ release. The inhibitory effect of Ca2+ was most marked when a sub-optimal concentration of InsP3 was used. An increase in extravesicular pH produced a decrease in the concentration of InsP3 that yielded half-maximal Ca2+ release. Regulation of the affinity of the InsP3 receptor by Ca2+ and pH can qualitatively account for the observed effects of these factors on InsP3-mediated Ca2+ release. Feedback inhibition of InsP3 binding by Ca2+ could provide a mechanism to generate Ca2+ oscillations, particularly under hormonal conditions that produce sub-optimal elevations of InsP3 concentration.

MeSH Terms
Animals Binding Sites Calcium/metabolism,pharmacology Cerebellum/metabolism Hydrogen-Ion Concentration Inositol 1,4,5-Trisphosphate Inositol Phosphates/metabolism Kinetics Microsomes/metabolism Rats Sugar Phosphates/metabolism
Chemicals
Inositol Phosphates Sugar Phosphates Inositol 1,4,5-Trisphosphate Calcium
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Joseph S K
Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia 19104.
Rice H L
Williamson J R
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Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
0264-6021
DOI
10.1042/bj2580261
Published
1989-02-15
Pages
261-5
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1138349
Subset
IM
Grants
NIDDK NIH HHS · DK-14461 · United States
NIDDK NIH HHS · DK-34804 · United States
External Links
PubMed source DOI: 10.1042/bj2580261 PMC Full Text View journal details
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