{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1363388844410694016.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1152/ajpheart.00964.2009"}},{"identifier":{"@type":"URI","@value":"https://www.physiology.org/doi/pdf/10.1152/ajpheart.00964.2009"}},{"identifier":{"@type":"PMID","@value":"20173044"}}],"dc:title":[{"@value":"Knockout of Na<sup>+</sup>/Ca<sup>2+</sup>exchanger in smooth muscle attenuates vasoconstriction and L-type Ca<sup>2+</sup>channel current and lowers blood pressure"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p>Mice with smooth muscle (SM)-specific knockout of Na<jats:sup>+</jats:sup>/Ca<jats:sup>2+</jats:sup>exchanger type-1 (NCX1<jats:sup>SM−/−</jats:sup>) and the NCX inhibitor, SEA0400, were used to study the physiological role of NCX1 in mouse mesenteric arteries. NCX1 protein expression was greatly reduced in arteries from NCX1<jats:sup>SM−/−</jats:sup>mice generated with Cre recombinase. Mean blood pressure (BP) was 6–10 mmHg lower in NCX1<jats:sup>SM−/−</jats:sup>mice than in wild-type (WT) controls. Vasoconstriction was studied in isolated, pressurized mesenteric small arteries from WT and NCX1<jats:sup>SM−/−</jats:sup>mice and in heterozygotes with a global null mutation (NCX1<jats:sup>Fx/−</jats:sup>). Reduced NCX1 activity was manifested by a marked attenuation of responses to low extracellular Na<jats:sup>+</jats:sup>concentration, nanomolar ouabain, and SEA0400. Myogenic tone (MT, 70 mmHg) was reduced by ∼15% in NCX1<jats:sup>SM−/−</jats:sup>arteries and, to a similar extent, by SEA0400 in WT arteries. MT was normal in arteries from NCX1<jats:sup>Fx/−</jats:sup>mice, which had normal BP. Vasoconstrictions to phenylephrine and elevated extracellular K<jats:sup>+</jats:sup>concentration were significantly reduced in NCX1<jats:sup>SM−/−</jats:sup>arteries. Because a high extracellular K<jats:sup>+</jats:sup>concentration-induced vasoconstriction involves the activation of L-type voltage-gated Ca<jats:sup>2+</jats:sup>channels (LVGCs), we measured LVGC-mediated currents and Ca<jats:sup>2+</jats:sup>sparklets in isolated mesenteric artery myocytes. Both the currents and the sparklets were significantly reduced in NCX1<jats:sup>SM−/−</jats:sup>(vs. WT or NCX1<jats:sup>Fx/−</jats:sup>) myocytes, but the voltage-dependent inactivation of LVGCs was not augmented. An acute application of SEA0400 in WT myocytes had no effect on LVGC current. The LVGC agonist, Bay K 8644, eliminated the differences in LVGC currents and Ca<jats:sup>2+</jats:sup>sparklets between NCX1<jats:sup>SM−/−</jats:sup>and control myocytes, suggesting that LVGC expression was normal in NCX1<jats:sup>SM−/−</jats:sup>myocytes. Bay K 8644 did not, however, eliminate the difference in myogenic constriction between WT and NCX1<jats:sup>SM−/−</jats:sup>arteries. We conclude that, under physiological conditions, NCX1-mediated Ca<jats:sup>2+</jats:sup>entry contributes significantly to the maintenance of MT. In NCX1<jats:sup>SM−/−</jats:sup>mouse artery myocytes, the reduced Ca<jats:sup>2+</jats:sup>entry via NCX1 may lower cytosolic Ca<jats:sup>2+</jats:sup>concentration and thereby reduce MT and BP. The reduced LVGC activity may be the consequence of a low cytosolic Ca<jats:sup>2+</jats:sup>concentration.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1383388844410694153","@type":"Researcher","foaf:name":[{"@value":"Jin Zhang"}],"jpcoar:affiliationName":[{"@value":"Departments of 1Physiology and"}]},{"@id":"https://cir.nii.ac.jp/crid/1383388844410694150","@type":"Researcher","foaf:name":[{"@value":"Chongyu Ren"}],"jpcoar:affiliationName":[{"@value":"Departments of 1Physiology and"}]},{"@id":"https://cir.nii.ac.jp/crid/1383388844410694017","@type":"Researcher","foaf:name":[{"@value":"Ling Chen"}],"jpcoar:affiliationName":[{"@value":"Medicine, University of Maryland School of Medicine, Baltimore, Maryland;"}]},{"@id":"https://cir.nii.ac.jp/crid/1383388844410694147","@type":"Researcher","foaf:name":[{"@value":"Manuel F. Navedo"}],"jpcoar:affiliationName":[{"@value":"Department of Physiology and Biophysics, University of Washington, Seattle, Washington;"}]},{"@id":"https://cir.nii.ac.jp/crid/1383388844410694144","@type":"Researcher","foaf:name":[{"@value":"Laura K. Antos"}],"jpcoar:affiliationName":[{"@value":"Departments of 1Physiology and"}]},{"@id":"https://cir.nii.ac.jp/crid/1383388844410694152","@type":"Researcher","foaf:name":[{"@value":"Stephen P. Kinsey"}],"jpcoar:affiliationName":[{"@value":"Departments of 1Physiology and"}]},{"@id":"https://cir.nii.ac.jp/crid/1383388844410694151","@type":"Researcher","foaf:name":[{"@value":"Takahiro Iwamoto"}],"jpcoar:affiliationName":[{"@value":"Department of Pharmacology, Fukuoka University School of Medicine, Fukuoka, Japan;"}]},{"@id":"https://cir.nii.ac.jp/crid/1383388844410694145","@type":"Researcher","foaf:name":[{"@value":"Kenneth D. Philipson"}],"jpcoar:affiliationName":[{"@value":"Department of Physiology, David Geffen School of Medicine at the University of California, Los Angeles, California; and"}]},{"@id":"https://cir.nii.ac.jp/crid/1383388844410694148","@type":"Researcher","foaf:name":[{"@value":"Michael I. Kotlikoff"}],"jpcoar:affiliationName":[{"@value":"Department of Biomedical Sciences, Cornell University Veterinary College, Ithaca, New York"}]},{"@id":"https://cir.nii.ac.jp/crid/1383388844410694016","@type":"Researcher","foaf:name":[{"@value":"Luis F. Santana"}],"jpcoar:affiliationName":[{"@value":"Department of Physiology and Biophysics, University of Washington, Seattle, Washington;"}]},{"@id":"https://cir.nii.ac.jp/crid/1383388844410694146","@type":"Researcher","foaf:name":[{"@value":"W. Gil Wier"}],"jpcoar:affiliationName":[{"@value":"Departments of 1Physiology and"}]},{"@id":"https://cir.nii.ac.jp/crid/1383388844410694018","@type":"Researcher","foaf:name":[{"@value":"Donald R. Matteson"}],"jpcoar:affiliationName":[{"@value":"Departments of 1Physiology and"}]},{"@id":"https://cir.nii.ac.jp/crid/1383388844410694149","@type":"Researcher","foaf:name":[{"@value":"Mordecai P. Blaustein"}],"jpcoar:affiliationName":[{"@value":"Departments of 1Physiology and"},{"@value":"Medicine, University of Maryland School of Medicine, Baltimore, Maryland;"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"03636135"},{"@type":"EISSN","@value":"15221539"}],"prism:publicationName":[{"@value":"American Journal of Physiology-Heart and Circulatory Physiology"}],"dc:publisher":[{"@value":"American Physiological Society"}],"prism:publicationDate":"2010-05","prism:volume":"298","prism:number":"5","prism:startingPage":"H1472","prism:endingPage":"H1483"},"reviewed":"false","dcterms:accessRights":"http://purl.org/coar/access_right/c_abf2","url":[{"@id":"https://www.physiology.org/doi/pdf/10.1152/ajpheart.00964.2009"}],"createdAt":"2010-02-20","modifiedAt":"2025-02-18","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=Patch-Clamp%20Techniques","dc:title":"Patch-Clamp Techniques"},{"@id":"https://cir.nii.ac.jp/all?q=Calcium%20Channels,%20L-Type","dc:title":"Calcium Channels, L-Type"},{"@id":"https://cir.nii.ac.jp/all?q=Blotting,%20Western","dc:title":"Blotting, Western"},{"@id":"https://cir.nii.ac.jp/all?q=Green%20Fluorescent%20Proteins","dc:title":"Green Fluorescent Proteins"},{"@id":"https://cir.nii.ac.jp/all?q=Myocytes,%20Smooth%20Muscle","dc:title":"Myocytes, Smooth Muscle"},{"@id":"https://cir.nii.ac.jp/all?q=Blood%20Pressure","dc:title":"Blood Pressure"},{"@id":"https://cir.nii.ac.jp/all?q=Muscle,%20Smooth,%20Vascular","dc:title":"Muscle, Smooth, Vascular"},{"@id":"https://cir.nii.ac.jp/all?q=Sodium-Calcium%20Exchanger","dc:title":"Sodium-Calcium Exchanger"},{"@id":"https://cir.nii.ac.jp/all?q=Mice","dc:title":"Mice"},{"@id":"https://cir.nii.ac.jp/all?q=Animals","dc:title":"Animals"},{"@id":"https://cir.nii.ac.jp/all?q=Telemetry","dc:title":"Telemetry"},{"@id":"https://cir.nii.ac.jp/all?q=Calcium%20Signaling","dc:title":"Calcium Signaling"},{"@id":"https://cir.nii.ac.jp/all?q=Mice,%20Knockout","dc:title":"Mice, Knockout"},{"@id":"https://cir.nii.ac.jp/all?q=Aniline%20Compounds","dc:title":"Aniline Compounds"},{"@id":"https://cir.nii.ac.jp/all?q=Phenyl%20Ethers","dc:title":"Phenyl Ethers"},{"@id":"https://cir.nii.ac.jp/all?q=Arteries","dc:title":"Arteries"},{"@id":"https://cir.nii.ac.jp/all?q=3-Pyridinecarboxylic%20acid,%201,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-,%20Methyl%20ester","dc:title":"3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester"},{"@id":"https://cir.nii.ac.jp/all?q=Electrophysiology","dc:title":"Electrophysiology"},{"@id":"https://cir.nii.ac.jp/all?q=Mice,%20Inbred%20C57BL","dc:title":"Mice, Inbred C57BL"},{"@id":"https://cir.nii.ac.jp/all?q=Calcium%20Channel%20Agonists","dc:title":"Calcium Channel Agonists"},{"@id":"https://cir.nii.ac.jp/all?q=Vasoconstriction","dc:title":"Vasoconstriction"},{"@id":"https://cir.nii.ac.jp/all?q=Muscle%20Tonus","dc:title":"Muscle Tonus"},{"@id":"https://cir.nii.ac.jp/all?q=Indicators%20and%20Reagents","dc:title":"Indicators and Reagents"}],"relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360004237732850048","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Conditional knockout of smooth muscle sodium calcium exchanger type-1 lowers blood pressure and attenuates Angiotensin II-salt hypertension"}]},{"@id":"https://cir.nii.ac.jp/crid/1360285711295175808","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Overactive bladder mediated by accelerated Ca<sup>2+</sup> influx mode of Na<sup>+</sup>/Ca<sup>2+</sup> exchanger in smooth muscle"}]},{"@id":"https://cir.nii.ac.jp/crid/2051433317027251840","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Effect of heterozygous deletion of WNK1 on the WNK-OSR1/SPAK-NCC/NKCC1/NKCC2 signal cascade in the kidney and blood vessels"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1152/ajpheart.00964.2009"},{"@type":"OPENAIRE","@value":"doi_dedup___::abbb6486d1c7883529309f4c4505d40a"},{"@type":"CROSSREF","@value":"10.14814/phy2.12273_references_DOI_HaoKm7xLtFLuhNbZnqmWYnUhDys"},{"@type":"CROSSREF","@value":"10.1152/ajpcell.00065.2013_references_DOI_HaoKm7xLtFLuhNbZnqmWYnUhDys"},{"@type":"CROSSREF","@value":"10.1007/s10157-012-0590-x_references_DOI_HaoKm7xLtFLuhNbZnqmWYnUhDys"}]}