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dc.contributor.author
Cabral, Pablo D.
dc.contributor.author
Capurro, Claudia Graciela
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dc.contributor.author
Garvin, Jeffrey L.
dc.date.available
2017-03-17T17:48:02Z
dc.date.issued
2015-07
dc.identifier.citation
Cabral, Pablo D.; Capurro, Claudia Graciela; Garvin, Jeffrey L.; TRPV4 mediates flow-induced increases in intracellular Ca in medullary thick ascending limbs; Wiley; Acta Physiologica; 214; 3; 7-2015; 319-328
dc.identifier.issn
1748-1708
dc.identifier.uri
http://hdl.handle.net/11336/14018
dc.description.abstract
Medullary thick ascending limbs (mTAL) regulate Na balance and therefore blood pressure. We previously showed that cell swelling and luminal flow activates the mechanosensitive channel TRPV4 in mTAL. AIM: We hypothesized that TRPV4 mediates flow-induced increases in intracellular Ca (Cai) in rat mTALs. METHODS: We performed ratiometric measurements of Cai in perfused mTALs. RESULTS: Increasing luminal flow from 0 to 20 nL min−1 caused Cai to peak 231 ± 29 nmol L−1 above basal concentrations (n = 18). The general TRPV inhibitor ruthenium red at 15 and 50 μmol L−1 reduced peak Cai by 41 ± 9 (P < 0.01; n = 5) and 77 ± 10% (P < 0.02; n = 6). The selective TRPV4 inhibitor RN1734 at 10 and 50 μmol L−1 reduced peak Cai by 46 ± 11 (P < 0.01; n = 7) and 76 ± 5% (P < 0.02; n = 5) respectively. To specifically target TRPV4, mTALs were transduced with adenoviruses expressing TRPV4 small hairpin (sh) RNA. In non-transduced control mTALs, luminal flow generated a peak increase in Cai of 111 ± 21 nmol L−1 (n = 8). In TRPV4shRNA-transduced mTALs, the Cai peak was reduced to 56 ± 8 nmol L−1 (P < 0.03, n = 9). Removing extracellular Ca completely abolished flow-induced increases in Cai. Increasing luminal flow in the presence of hexokinase 20 (U mL−1) to scavenge extracellular ATP did not modify significantly the increases in Cai induced by luminal flow. Finally, we studied the effect of the TRPV4 selective agonist GSK1016790A on Cai. In the absence of luminal flow, GSK1016790A (10 nmol L−1) increased Cai from 60 ± 11 nmol L−1 to 262 ± 71 nmol L−1 (P < 0.05; n = 7). CONCLUSION: We conclude that flow-induced increases in Cai are mediated primarily by TRPV4 in the rat mTAL.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Wiley
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dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Mechanosensation
dc.subject
Trp Channels
dc.subject
Nitric Oxide
dc.subject.classification
Fisiología
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dc.subject.classification
Medicina Básica
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dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
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dc.title
TRPV4 mediates flow-induced increases in intracellular Ca in medullary thick ascending limbs
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2017-03-17T14:29:47Z
dc.identifier.eissn
1748-1716
dc.journal.volume
214
dc.journal.number
3
dc.journal.pagination
319-328
dc.journal.pais
Estados Unidos
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dc.journal.ciudad
Hoboken
dc.description.fil
Fil: Cabral, Pablo D.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina. Case Western Reserve University; Estados Unidos. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas; Argentina
dc.description.fil
Fil: Capurro, Claudia Graciela. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
dc.description.fil
Fil: Garvin, Jeffrey L.. Case Western Reserve University; Estados Unidos
dc.journal.title
Acta Physiologica
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dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1111/apha.12528/abstract
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1111/apha.12528
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