Endothelin-1 stimulates the Na+/Ca2+ exchanger reverse mode through intracellular Na+ (Na+i) - Dependent and Na+i-independent pathways

This study aimed to explore the signaling pathways involved in the positive inotropic effect (PIE) of low doses of endothelin-1 (ET-1). Cat papillary muscles were used for force and intracellular Na<SUP>+</SUP> concentration (Na<SUP>+</SUP><SUB>i</SUB>) measuremen...

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Detalles Bibliográficos
Autores principales: Aiello, Ernesto Alejandro, Villa Abrille, María Celeste, Dulce, Raúl Ariel, Cingolani, Horacio Eugenio, Pérez, Néstor Gustavo
Formato: Articulo
Lenguaje:Inglés
Publicado: 2005
Materias:
Ciencias Médicas
Contraction
Endothelin
Ion channels
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/84302
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-84302
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Médicas
Contraction
Endothelin
Ion channels
spellingShingle Ciencias Médicas
Contraction
Endothelin
Ion channels
Aiello, Ernesto Alejandro
Villa Abrille, María Celeste
Dulce, Raúl Ariel
Cingolani, Horacio Eugenio
Pérez, Néstor Gustavo
Endothelin-1 stimulates the Na+/Ca2+ exchanger reverse mode through intracellular Na+ (Na+i) - Dependent and Na+i-independent pathways
topic_facet Ciencias Médicas
Contraction
Endothelin
Ion channels
description This study aimed to explore the signaling pathways involved in the positive inotropic effect (PIE) of low doses of endothelin-1 (ET-1). Cat papillary muscles were used for force and intracellular Na<SUP>+</SUP> concentration (Na<SUP>+</SUP><SUB>i</SUB>) measurements, and isolated cat ventricular myocytes for patch-clamp experiments. ET-1 (5 nmol/L) induced a PIE and an associated increase in Na<SUP>+</SUP><SUB>i</SUB> that were abolished by Na +/H+ exchanger (NHE) inhibition with HOE642. Reverse-mode Na<SUP>+</SUP>/Ca<SUP>2+</SUP> exchanger (NCX) blockade with KB-R7943 reversed the ET-1-induced PIE. These results suggest that the ET-1-induced PIE is totally attributable to the NHE-mediated Na<SUP>+</SUP><SUB>i</SUB> increase. However, an additional direct stimulating effect of ET-1 on NCX after the necessary increase in Na<SUP>+</SUP><SUB>i</SUB> could occur. Thus, the ET-1-induced increase in Na<SUP>+</SUP><SUB>i</SUB> and contractility was compared with that induced by partial inhibition of the Na<SUP>+</SUP>/K<SUP>+</SUP> ATPase by lowering extracellular K<SUP>+</SUP> (K<SUP>+</SUP><SUB>o</SUB>) For a given Na<SUP>+</SUP><SUB>i</SUB>, ET-1 induced a greater PIE than low K<SUP>+</SUP><SUB>o</SUB>. In the presence of HOE642 and after increasing contractility and Na<SUP>+</SUP><SUB>i</SUB> by low K<SUP>+</SUP><SUB>o</SUB>, ET-1 induced an additional PIE that was reversed by KB-R7943 or the protein kinase C (PKC) inhibitor chelerythrine. ET-1 increased the NCX current and negatively shifted the NCX reversal potential (E<SUB>NCX</SUB>). HOE642 attenuated the increase in NCX outward current and abolished the E<SUB>NCX</SUB> shift. These results indicate that whereas the NHE-mediated ET-1-induced increase in Na<SUP>+</SUP><SUB>i</SUB> seems to be mandatory to drive NCX in reverse and enhance contractility, Na<SUP>+</SUP><SUB>i</SUB>-independent and PKC-dependent NCX stimulation appears to additionally contribute to the PIE. However, it is important to stress that the latter can only occur after the primary participation of the former.
format Articulo
Articulo
author Aiello, Ernesto Alejandro
Villa Abrille, María Celeste
Dulce, Raúl Ariel
Cingolani, Horacio Eugenio
Pérez, Néstor Gustavo
author_facet Aiello, Ernesto Alejandro
Villa Abrille, María Celeste
Dulce, Raúl Ariel
Cingolani, Horacio Eugenio
Pérez, Néstor Gustavo
author_sort Aiello, Ernesto Alejandro
title Endothelin-1 stimulates the Na+/Ca2+ exchanger reverse mode through intracellular Na+ (Na+i) - Dependent and Na+i-independent pathways
title_short Endothelin-1 stimulates the Na+/Ca2+ exchanger reverse mode through intracellular Na+ (Na+i) - Dependent and Na+i-independent pathways
title_full Endothelin-1 stimulates the Na+/Ca2+ exchanger reverse mode through intracellular Na+ (Na+i) - Dependent and Na+i-independent pathways
title_fullStr Endothelin-1 stimulates the Na+/Ca2+ exchanger reverse mode through intracellular Na+ (Na+i) - Dependent and Na+i-independent pathways
title_full_unstemmed Endothelin-1 stimulates the Na+/Ca2+ exchanger reverse mode through intracellular Na+ (Na+i) - Dependent and Na+i-independent pathways
title_sort endothelin-1 stimulates the na+/ca2+ exchanger reverse mode through intracellular na+ (na+i) - dependent and na+i-independent pathways
publishDate 2005
url http://sedici.unlp.edu.ar/handle/10915/84302
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