The store-operated calcium-release-activated calcium current, ICRAC, is a major mechanism for calcium entry into non-excitable cells. ICRAC refills calcium stores and permits sustained calcium signalling. The relationship between inositol 1,4,5-trisphosphate receptor (InsP3R)-containing stores and ICRAC is not understood. A model of global InsP3R store depletion coupling with ICRAC activation may be simplistic, since intracellular stores are heterogeneous in their release and refilling activities. Here we use a ligand-gated calcium channel, TRPV1 (transient receptor potential channel, vanilloid subfamily member 1), as a new tool to probe store heterogeneity and define intracellular calcium compartments in a mast cell line. TRPV1 has activity as an intracellular release channel but does not mediate global calcium store depletion and does not invade a store coupled with ICRAC. Intracellular TRPV1 localizes to a subset of the InsP3R-containing stores. TRPV1 sensitivity functionally subdivides the InsP3-sensitive store, as does heterogeneity in the sarcoplasmic/endoplasmic-reticulum Ca2+-ATPase isoforms responsible for store refilling. These results provide unequivocal evidence that a specific ‘CRAC store’ exists within the InsP3-releasable calcium stores and describe a novel methodology for manipulation of intracellular free calcium.
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April 2003
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Research Article|
April 15 2003
Discrimination of intracellular calcium store subcompartments using TRPV1 (transient receptor potential channel, vanilloid subfamily member 1) release channel activity
Helen TURNER;
Helen TURNER
1
∗Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, U.S.A.
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Andrea FLEIG;
Andrea FLEIG
∗Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, U.S.A.
†Laboratory of Cell and Molecular Signaling, Center for Biomedical Research at the Queen's Medical Center, University Tower 8, 1301 Punchbowl Street, Honolulu, HI 96813, U.S.A.
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Alexander STOKES;
Alexander STOKES
1
‡Laboratory of Allergy and Immunology, Department of Pathology, Harvard Medical School and Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, U.S.A.
2To whom correspondence should be addressed (e-mail rpenner@hawaii.edu).
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Jean-Pierre KINET;
Jean-Pierre KINET
‡Laboratory of Allergy and Immunology, Department of Pathology, Harvard Medical School and Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, U.S.A.
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Reinhold PENNER
Reinhold PENNER
2
∗Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, U.S.A.
†Laboratory of Cell and Molecular Signaling, Center for Biomedical Research at the Queen's Medical Center, University Tower 8, 1301 Punchbowl Street, Honolulu, HI 96813, U.S.A.
2To whom correspondence should be addressed (e-mail rpenner@hawaii.edu).
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Publisher: Portland Press Ltd
Received:
September 02 2002
Revision Received:
December 05 2002
Accepted:
January 06 2003
Accepted Manuscript online:
January 06 2003
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2003
2003
Biochem J (2003) 371 (2): 341–350.
Article history
Received:
September 02 2002
Revision Received:
December 05 2002
Accepted:
January 06 2003
Accepted Manuscript online:
January 06 2003
Citation
Helen TURNER, Andrea FLEIG, Alexander STOKES, Jean-Pierre KINET, Reinhold PENNER; Discrimination of intracellular calcium store subcompartments using TRPV1 (transient receptor potential channel, vanilloid subfamily member 1) release channel activity. Biochem J 15 April 2003; 371 (2): 341–350. doi: https://doi.org/10.1042/bj20021381
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