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PMID: 9065781 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Ca2+ differentially regulates the ligand-affinity states of type 1 and type 3 inositol 1,4,5-trisphosphate receptors.

The Biochemical journal ·Vol. 322 ( Pt 2) ·1997-03-01 ·Pages 591-6

Yoneshima H, Miyawaki A, Michikawa T, Furuichi T, Mikoshiba K

Abstract

To elucidate the functional difference between type 1 and type 3 Ins(1,4,5)P3 receptors [Ins(1,4,5)P3R1 and Ins(1,4,5)P3R3 respectively] we studied the effect of Ca2+ on the ligand-binding properties of both Ins(1,4,5)P3R types. We expressed full-length human Ins(1,4,5)P3R1 and Ins(1,4,5)P3R3 from cDNA species in insect ovary Sf9 cells, and the membrane fractions were used for Ins(1,4,5)P3-binding assays. The binding of Ins(1,4,5)P3 to Ins(1,4,5)P3R1 and Ins(1,4,5)P3R3 was differentially regulated by Ca2+. With increasing concentrations of free Ca2+ ([Ca2+]), Ins(1,4,5)P3 binding to Ins(1,4,5)P2R1 decreased, whereas that to Ins(1,4,5)P3R3 increased. Alteration of Ins(1,4,5)P3 binding to Ins(1,4,5)P3R1 was observed at [Ca2+] ranging from less than 1 nM to more than 10 microM. The EC50 of Ins(1,4,5)P3 binding was 100 nM Ca2+ for Ins(1,4,5)P3R1. In contrast, Ins(1,4,5)P3 binding to Ins(1,4,5)P3R3 was changed at high [Ca2+] with an EC50 value of 872 nM, and steeply between 100 nM and 10 microM. These Ca2+-dependent alterations of Ins(1,4,5)P3 binding to both Ins(1,4,5)P3R types were reversible. Scatchard analyses revealed that Ca2+ changed the affinity of both Ins(1,4,5)P3R types but not the total number of Ins(1,4,5)P3-binding sites. The Kd values of Ins(1,4,5)P3R1 for Ins(1,4,5)P3 were 78.5 nM with 3 nM free Ca2+, and 312 nM with 1.4 microM free Ca2+. In contrast, Ins(1,4,5)P3R3 exhibited an affinity for Ins(1,4,5)P3 with Kd values of 116 nM with 3 nM free Ca2+, and 62.2 nM with 1.4 microM free Ca2+. These results indicate that (1) both Ins(1,4,5)P3R1 and Ins(1,4,5)P3R3 have at least two affinity states, (2) Ca2+ regulates interconversions between these states, and (3) Ca2+ regulates the binding of Ins(1,4,5)P3 to Ins(1,4,5)P3R1 and Ins(1,4,5)P3R3 in opposite manners.

MeSH Terms
Calcium/pharmacology Calcium Channels/biosynthesis,classification,drug effects Chelating Agents/pharmacology Dose-Response Relationship, Drug Egtazic Acid/pharmacology Humans Inositol 1,4,5-Trisphosphate/metabolism Inositol 1,4,5-Trisphosphate Receptors Ligands Receptors, Cytoplasmic and Nuclear/biosynthesis,classification,drug effects Recombinant Proteins/drug effects
Chemicals
Calcium Channels Chelating Agents ITPR1 protein, human Inositol 1,4,5-Trisphosphate Receptors Ligands Receptors, Cytoplasmic and Nuclear Recombinant Proteins Egtazic Acid Inositol 1,4,5-Trisphosphate Calcium
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Yoneshima H
Department of Molecular Neurobiology, University of Tokyo, Japan.
Miyawaki A
Michikawa T
Furuichi T
Mikoshiba K
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Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
0264-6021
DOI
10.1042/bj3220591
Published
1997-03-01
Pages
591-6
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1218230
Subset
IM
External Links
PubMed source DOI: 10.1042/bj3220591 PMC Full Text View journal details
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