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Artículo

Inhibition of carbonic anhydrase prevents the Na /H exchanger 1-dependent slow force response to rat myocardial stretch

Vargas, Lorena AlejandraIcon ; Diaz, Romina GiselIcon ; Swenson, Erik R.; Perez, Nestor GustavoIcon ; Alvarez, BernardoIcon
Fecha de publicación: 07/2013
Editorial: American Physiological Society
Revista: American Journal Of Physiology-heart And Circulatory Physiology
ISSN: 0363-6135
e-ISSN: 1522-1539
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Fisiología

Resumen

Myocardial stretch is an established signal that leads to hypertrophy. Myocardial stretch induces a first immediate force increase followed by a slow force response (SFR), which is a consequence of an increased Ca2+ transient that follows the NHE1 Na+/H+ exchanger activation. Carbonic anhydrase II (CAII) binds to the extreme COOH terminus of NHE1 and regulates its transport activity. We aimed to test the role of CAII bound to NHE1 in the SFR. The SFR and changes in intracellular pH (pHi) were evaluated in rat papillary muscle bathed with CO2/HCO3− buffer and stretched from 92% to 98% of the muscle maximal force development length for 10 min in the presence of the CA inhibitor 6-ethoxzolamide (ETZ, 100 μM). SFR control was 120 ± 3% (n = 8) of the rapid initial phase and was fully blocked by ETZ (99 ± 4%, n = 6). The SFR corresponded to a maximal increase in pHi of 0.18 ± 0.02 pH units (n = 4), and pHi changes were blocked by ETZ (0.04 ± 0.04, n = 6), as monitored by epifluorescence. NHE1/CAII physical association was examined in the SFR by coimmunoprecipitation, using muscle lysates. CAII immunoprecipitated with an anti-NHE1 antibody and the CAII immunoprecipitated protein levels increased 58 ± 9% (n = 6) upon stretch of muscles, assessed by immunoblots. The p90RSK kinase inhibitor SL0101–1 (10 μM) blocked the SFR of heart muscles after stretch 102 ± 2% (n = 4) and reduced the binding of CAII to NHE1, suggesting that the stretch-induced phosphorylation of NHE1 increases its binding to CAII. CAII/NHE1 interaction constitutes a component of the SFR to heart muscle stretch, which potentiates NHE1-mediated H+ transport in the myocardium.
Palabras clave: Stretch , Carbonic Anhydrase Ii , Slow Force Response
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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)
Identificadores
URI: http://hdl.handle.net/11336/11951
DOI: http://dx.doi.org/10.1152/ajpheart.00055.2013
URL: http://ajpheart.physiology.org/content/305/2/H228
Colecciones
Articulos(CIC)
Articulos de CENTRO DE INVEST.CARDIOVASCULARES (I)
Citación
Vargas, Lorena Alejandra; Diaz, Romina Gisel; Swenson, Erik R.; Perez, Nestor Gustavo; Alvarez, Bernardo; Inhibition of carbonic anhydrase prevents the Na /H exchanger 1-dependent slow force response to rat myocardial stretch; American Physiological Society; American Journal Of Physiology-heart And Circulatory Physiology; 305; 2; 7-2013; 228-237
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