File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Multiple ryanodine receptor subtypes and heterogeneous ryanodine receptor-gated Ca 2+ stores in pulmonary arterial smooth muscle cells

TitleMultiple ryanodine receptor subtypes and heterogeneous ryanodine receptor-gated Ca 2+ stores in pulmonary arterial smooth muscle cells
Authors
KeywordsCalcium signaling
Calcium sparks
Intralobar pulmonary arteries
Perinuclear sarcoplasmic reticulum
Ryanodine receptors
Issue Date2005
PublisherAmerican Physiological Society. The Journal's web site is located at http://intl-ajplung.physiology.org/
Citation
American Journal Of Physiology - Lung Cellular And Molecular Physiology, 2005, v. 289 n. 2 33-2, p. L338-L348 How to Cite?
AbstractRyanodine receptors (RyRs) of pulmonary arterial smooth muscle cells (PASMCs) play important roles in major physiological processes such as hypoxic pulmonary vasoconstriction and perinatal pulmonary vasodilatation. Recent studies show that three subtypes of RyRs are coexpressed and RyR-gated Ca 2+ stores are distributed heterogeneously in systemic vascular myocytes. However, the molecular identity and subcellular distribution of RyRs have not been examined in PASMCs. In this study we detected mRNA and proteins of all three subtypes in rat intralobar PASMCs using RT-PCR and Western blot. Quantitative real-time RT-PCR showed that RyR2 mRNA was most abundant, ∼15-20 times more than the other two subtypes. Confocal fluorescence microscopy revealed that RyRs labeled with BODIPY TR-X ryanodine were localized in the peripheral and perinuclear regions and were colocalized with sarcoplasmic reticulum labeled with Fluo-5N. Immunostaining showed that the subsarcolemmal regions exhibited clear signals of RyR1 and RyR2, whereas the perinuclear compartments contained mainly RyR1 and RyR3. Ca 2+ sparks were recorded in both regions, and their activities were enhanced by a subthreshold concentration of caffeine or by endothelin-1, indicating functional RyR-gated Ca 2+ stores. Moreover, 18% of the perinuclear sparks were prolonged [full duration/half-maximum (FDHM) = 193.3 ± 22.6 ms] with noninactivating kinetics, in sharp contrast to the typical fast inactivating Ca 2+ sparks (FDHM = 44.6 ± 3.2 ms) recorded in the same PASMCs. In conclusion, multiple RyR subtypes are expressed differentially in peripheral and perinuclear RyR-gated Ca 2+ stores; the molecular-complexity and spatial heterogeneity of RyRs may facilitate specific Ca 2+ regulation of cellular functions in PASMCs. Copyright © 2005 the American Physiological Society.
Persistent Identifierhttp://hdl.handle.net/10722/80198
ISSN
2015 Impact Factor: 4.721
2015 SCImago Journal Rankings: 1.838
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorYang, XRen_HK
dc.contributor.authorLin, MJen_HK
dc.contributor.authorYip, KPen_HK
dc.contributor.authorJeyakumar, LHen_HK
dc.contributor.authorFleischer, Sen_HK
dc.contributor.authorLeung, GPHen_HK
dc.contributor.authorSham, JSKen_HK
dc.date.accessioned2010-09-06T08:03:36Z-
dc.date.available2010-09-06T08:03:36Z-
dc.date.issued2005en_HK
dc.identifier.citationAmerican Journal Of Physiology - Lung Cellular And Molecular Physiology, 2005, v. 289 n. 2 33-2, p. L338-L348en_HK
dc.identifier.issn1040-0605en_HK
dc.identifier.urihttp://hdl.handle.net/10722/80198-
dc.description.abstractRyanodine receptors (RyRs) of pulmonary arterial smooth muscle cells (PASMCs) play important roles in major physiological processes such as hypoxic pulmonary vasoconstriction and perinatal pulmonary vasodilatation. Recent studies show that three subtypes of RyRs are coexpressed and RyR-gated Ca 2+ stores are distributed heterogeneously in systemic vascular myocytes. However, the molecular identity and subcellular distribution of RyRs have not been examined in PASMCs. In this study we detected mRNA and proteins of all three subtypes in rat intralobar PASMCs using RT-PCR and Western blot. Quantitative real-time RT-PCR showed that RyR2 mRNA was most abundant, ∼15-20 times more than the other two subtypes. Confocal fluorescence microscopy revealed that RyRs labeled with BODIPY TR-X ryanodine were localized in the peripheral and perinuclear regions and were colocalized with sarcoplasmic reticulum labeled with Fluo-5N. Immunostaining showed that the subsarcolemmal regions exhibited clear signals of RyR1 and RyR2, whereas the perinuclear compartments contained mainly RyR1 and RyR3. Ca 2+ sparks were recorded in both regions, and their activities were enhanced by a subthreshold concentration of caffeine or by endothelin-1, indicating functional RyR-gated Ca 2+ stores. Moreover, 18% of the perinuclear sparks were prolonged [full duration/half-maximum (FDHM) = 193.3 ± 22.6 ms] with noninactivating kinetics, in sharp contrast to the typical fast inactivating Ca 2+ sparks (FDHM = 44.6 ± 3.2 ms) recorded in the same PASMCs. In conclusion, multiple RyR subtypes are expressed differentially in peripheral and perinuclear RyR-gated Ca 2+ stores; the molecular-complexity and spatial heterogeneity of RyRs may facilitate specific Ca 2+ regulation of cellular functions in PASMCs. Copyright © 2005 the American Physiological Society.en_HK
dc.languageengen_HK
dc.publisherAmerican Physiological Society. The Journal's web site is located at http://intl-ajplung.physiology.org/en_HK
dc.relation.ispartofAmerican Journal of Physiology - Lung Cellular and Molecular Physiologyen_HK
dc.subjectCalcium signalingen_HK
dc.subjectCalcium sparksen_HK
dc.subjectIntralobar pulmonary arteriesen_HK
dc.subjectPerinuclear sarcoplasmic reticulumen_HK
dc.subjectRyanodine receptorsen_HK
dc.titleMultiple ryanodine receptor subtypes and heterogeneous ryanodine receptor-gated Ca 2+ stores in pulmonary arterial smooth muscle cellsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1040-0605&volume=289&spage=338&epage=348&date=2005&atitle=Multiple+ryanodine+receptor+subtypes+and+heterogeneous+ryanodine+receptor-gated+Ca+2++stores+in+pulmonary+arterial+smooth+muscle+cellsen_HK
dc.identifier.emailLeung, GPH: gphleung@hkucc.hku.hken_HK
dc.identifier.authorityLeung, GPH=rp00234en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1152/ajplung.00328.2004en_HK
dc.identifier.pmid15863441en_HK
dc.identifier.scopuseid_2-s2.0-22444449203en_HK
dc.identifier.hkuros103545en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-22444449203&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume289en_HK
dc.identifier.issue2 33-2en_HK
dc.identifier.spageL338en_HK
dc.identifier.epageL348en_HK
dc.identifier.isiWOS:000230328000022-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridYang, XR=8504673700en_HK
dc.identifier.scopusauthoridLin, MJ=37042017600en_HK
dc.identifier.scopusauthoridYip, KP=7101909682en_HK
dc.identifier.scopusauthoridJeyakumar, LH=6603578806en_HK
dc.identifier.scopusauthoridFleischer, S=7103394420en_HK
dc.identifier.scopusauthoridLeung, GPH=35963668200en_HK
dc.identifier.scopusauthoridSham, JSK=21738467300en_HK

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats