Skip to content

Research at St Andrews

Identification of Functionally Segregated Sarcoplasmic Reticulum Calcium Stores in Pulmonary Arterial Smooth Muscle

Research output: Contribution to journalArticlepeer-review

DOI

Author(s)

Jill H. Clark, Nicholas Patrick Kinnear, Svetlana Kalujnaia, Gordon Cramb, Sidney Fleischer, Loice H. Jeyakumar, Frank Wuytack, A. Mark Evans

School/Research organisations

Abstract

In pulmonary arterial smooth muscle, Ca2+ release from the sarcoplasmic reticulum (SR) via ryanodine receptors (RyRs) may induce constriction and dilation in a manner that is not mutually exclusive. We show here that the targeting of different sarcoplasmic/endoplasmic reticulum Ca2+-ATPases (SERCA) and RyR subtypes to discrete SR regions explains this paradox. Western blots identified protein bands for SERCA2a and SERCA2b, whereas immunofluorescence labeling of isolated pulmonary arterial smooth muscle cells revealed striking differences in the spatial distribution of SERCA2a and SERCA2b and RyR1, RyR2, and RyR3, respectively. Almost all SERCA2a and RyR3 labeling was restricted to a region within 1.5 mu m of the nucleus. In marked contrast, SERCA2b labeling was primarily found within 1.5 mu m of the plasma membrane, where labeling for RyR1 was maximal. The majority of labeling for RyR2 lay in between these two regions of the cell. Application of the vasoconstrictor endothelin-1 induced global Ca2+ waves in pulmonary arterial smooth muscle cells, which were markedly attenuated upon depletion of SR Ca2+ stores by preincubation of cells with the SERCA inhibitor thapsigargin but remained unaffected after preincubation of cells with a second SERCA antagonist, cyclopiazonic acid. We conclude that functionally segregated SR Ca2+ stores exist within pulmonary arterial smooth muscle cells. One sits proximal to the plasma membrane, receives Ca2+ via SERCA2b, and likely releases Ca2+ via RyR1 to mediate vasodilation. The other is located centrally, receives Ca2+ via SERCA2a, and likely releases Ca2+ via RyR3 and RyR2 to initiate vasoconstriction.

Close

Details

Original languageEnglish
Pages (from-to)13542-13549
Number of pages8
JournalJournal of Biological Chemistry
Volume285
Issue number18
DOIs
Publication statusPublished - 30 Apr 2010

    Research areas

  • ADENINE-DINUCLEOTIDE PHOSPHATE, DISTINCT CA2+ STORES, CYCLIC ADP-RIBOSE, ENDOPLASMIC-RETICULUM, CYCLOPIAZONIC ACID, CA2+-ATPASE SERCA, SKELETAL-MUSCLE, CA-2+ PUMP, MOLECULAR-CLONING, CA-2+-ATPASE GENE

Discover related content
Find related publications, people, projects and more using interactive charts.

View graph of relations

Related by author

  1. Cloning, tissue distribution and sub-cellular localisation of phospholipase C X-domain containing protein (PLCXD) isoforms

    Gellatly, S. A., Kalujnaia, S. & Cramb, G., 10 Aug 2012, In: Biochemical and Biophysical Research Communications. 424, 4, p. 651-656 6 p.

    Research output: Contribution to journalArticlepeer-review

  2. Differential timing of gene expression regulation between leptocephali of the two Anguilla eel species in the Sargasso Sea

    Bernatchez, L., St-Cyr, J., Normandeau, E., Maes, G., Als, T., Kalujnaia, S., Cramb, G., Castonguay, M. & Hansen, M., Dec 2011, In: Ecology and Evolution. 1, 4, p. 459-467 9 p.

    Research output: Contribution to journalArticlepeer-review

  3. A role for inositol monophosphatase 1 (IMPA1) in salinity adaptation in the euryhaline eel (Anguilla anguilla)

    Kalujnaia, S., McVee, J., Kasciukovic, T., Stewart, A. J. & Cramb, G., Oct 2010, In: FASEB Journal. 24, p. 3981-3991 11 p.

    Research output: Contribution to journalArticlepeer-review

Related by journal

  1. Journal of Biological Chemistry (Journal)

    Simon John Powis (Member of editorial board)

    1 Jun 2015

    Activity: Publication peer-review and editorial work typesEditor of research journal

  2. Journal of Biological Chemistry (Journal)

    Terry K Smith (Member of editorial board)

    2006 → …

    Activity: Publication peer-review and editorial work typesPeer review of manuscripts

Related by journal

  1. Iron is a ligand of SecA-like metal-binding domains in vivo

    Cranford-Smith, T., Jamshad, M., Jeeves, M., Chandler, R. A., Yule, J., Robinson, A., Alam, F., Dunne, K. A., Aponte Angarita, E. H., Alanazi, M., Carter, C., Henderson, I. R., Lovett, J. E., Winn, P., Knowles, T. & Huber, D., 2 Apr 2020, In: Journal of Biological Chemistry. Papers in Press

    Research output: Contribution to journalArticlepeer-review

  2. The tetraspanin Tspan15 is an essential subunit of an ADAM10 scissor complex

    Koo, C. Z., Harrison, N., Noy, P. J., Szyroka, J., Matthews, A. L., Hsia, H-E., Müller, S. A., Tüshaus, J., Goulding, J., Willis, K., Apicella, C., Cragoe, B., Davis, E., Keles, M., Malinova, A., McFarlane, T. A., Morrison, P. R., Nguyen, H. T. H., Sykes, M. C., Ahmed, H. & 11 others, Di Maio, A., Seipold, L., Saftig, P., Cull, E., Pliotas, C., Rubinstein, E., Poulter, N. S., Briddon, S. J., Holliday, N. D., Lichtenthaler, S. F. & Tomlinson, M. G., 28 Feb 2020, In: Journal of Biological Chemistry.

    Research output: Contribution to journalArticlepeer-review

  3. Combining SPR with atomic-force microscopy enables singlemolecule insights into activation and suppression of the complement cascade

    Makou, E., Bailey, R. G., Johnston, H., Parkin, J. D., Hulme, A. N., Hähner, G. & Barlow, P. N., 27 Dec 2019, In: Journal of Biological Chemistry. 294, 52, p. 20148-20163 16 p.

    Research output: Contribution to journalArticlepeer-review

  4. Dysregulated Zn2+ homeostasis impairs cardiac type-2 ryanodine receptor and mitsugumin 23 functions, leading to sarcoplasmic reticulum Ca2+ leakage

    Reilly-O'Donnell, B., Robertson, G. B., Karumbi, A., McIntyre, C., Bal, W., Nishi, M., Takeshima, H., Stewart, A. J. & Pitt, S. J., 11 Aug 2017, In: Journal of Biological Chemistry. 292, 32, p. 13361-13373 13 p.

    Research output: Contribution to journalArticlepeer-review

  5. The major histocompatibility complex class I immunopeptidome of extracellular vesicles

    Synowsky, S. A., Shirran, S. L., Cooke, F. G. M., Antoniou, A. N., Botting, C. H. & Powis, S. J., 13 Oct 2017, In: Journal of Biological Chemistry. 292, p. 17084-17092

    Research output: Contribution to journalArticlepeer-review

ID: 1238295

Top