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PMID: 7724546 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Calmodulin is a selective mediator of Ca(2+)-induced Ca2+ release via the ryanodine receptor-like Ca2+ channel triggered by cyclic ADP-ribose.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 92 ·No. 8 ·1995-04-11 ·Pages 3244-8

Tanaka Y, Tashjian AH

Abstract

The ryanodine receptor-like Ca2+ channel (RyRLC) is responsible for Ca2+ wave propagation and Ca2+ oscillations in certain nonmuscle cells by a Ca(2+)-induced Ca2+ release (CICR) mechanism. Cyclic ADP-ribose (cADPR), an enzymatic product derived from NAD+, is the only known endogenous metabolite that acts as an agonist on the RyRLC. However, the mode of action of cADPR is not clear. We have identified calmodulin as a functional mediator of cADPR-triggered CICR through the RyRLC in sea urchin eggs. cADPR-induced Ca2+ release consisted of two phases, an initial rapid release phase and a subsequent slower release. The second phase was selectively potentiated by calmodulin which, in turn, was activated by Ca2+ released during the initial phase. Caffeine enhanced the action of calmodulin. Calmodulin did not play a role in inositol 1,4,5-trisphosphate-induced Ca2+ release. These findings offer insights into the multiple pathways that regulate intracellular Ca2+ signaling.

MeSH Terms
Adenosine Diphosphate Ribose/analogs & derivatives,pharmacology Animals Caffeine/pharmacology Calcium/metabolism Calcium Channel Agonists/pharmacology Calcium Channels/drug effects Calmodulin/antagonists & inhibitors,pharmacology Cyclic ADP-Ribose Dose-Response Relationship, Drug Drug Interactions Models, Biological Muscle Proteins/drug effects Ovum/metabolism Ryanodine Receptor Calcium Release Channel Sea Urchins Subcellular Fractions/metabolism Sulfonamides/pharmacology
Chemicals
Calcium Channel Agonists Calcium Channels Calmodulin Muscle Proteins Ryanodine Receptor Calcium Release Channel Sulfonamides Cyclic ADP-Ribose Adenosine Diphosphate Ribose Caffeine W 7 N-(6-aminohexyl)-1-naphthalenesulfonamide Calcium
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Tanaka Y
Department of Molecular and Cellular Toxicology, Harvard School of Public Health, Harvard Medical School, Boston, MA 02115, USA.
Tashjian A H
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.92.8.3244
Published
1995-04-11
Pages
3244-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC42142
Subset
IM
Grants
NIDDK NIH HHS · DK 11011 · United States
External Links
PubMed source DOI: 10.1073/pnas.92.8.3244 PMC Full Text View journal details
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