The functional association between the sodium/bicarbonate cotransporter (NBC) and the soluble adenylyl cyclase (sAC) modulates cardiac contractility

The soluble adenylyl cyclase (sAC) was identified in the heart as another source of cyclic AMP (cAMP). However, its cardiac physiological function is unknown. On the other hand, the cardiac Na⁺/HCO₃⁻ cotransporter (NBC) promotes the cellular co-influx of HCO₃⁻ and Na⁺. Since sAC activity is regulate...

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Detalles Bibliográficos
Autores principales: Espejo, María Sofía, Orlowski, Alejandro, Ibañez, Alejandro Martín, Di Mattia, Romina Alejandra, Carrizo Velásquez, Fernanda Elisabeth, Rossetti, Noelia S., Ciancio, María Carolina, De Giusti, Verónica Celeste, Aiello, Ernesto Alejandro
Formato: Articulo
Lenguaje:Inglés
Publicado: 2020
Materias:
Ciencias Médicas
cAMP
Cardiac myocytes
Sodium/bicarbonate cotransporter
Soluble adenylyl cyclase
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/138261
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-138261
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
cAMP
Cardiac myocytes
Sodium/bicarbonate cotransporter
Soluble adenylyl cyclase
spellingShingle Ciencias Médicas
cAMP
Cardiac myocytes
Sodium/bicarbonate cotransporter
Soluble adenylyl cyclase
Espejo, María Sofía
Orlowski, Alejandro
Ibañez, Alejandro Martín
Di Mattia, Romina Alejandra
Carrizo Velásquez, Fernanda Elisabeth
Rossetti, Noelia S.
Ciancio, María Carolina
De Giusti, Verónica Celeste
Aiello, Ernesto Alejandro
The functional association between the sodium/bicarbonate cotransporter (NBC) and the soluble adenylyl cyclase (sAC) modulates cardiac contractility
topic_facet Ciencias Médicas
cAMP
Cardiac myocytes
Sodium/bicarbonate cotransporter
Soluble adenylyl cyclase
description The soluble adenylyl cyclase (sAC) was identified in the heart as another source of cyclic AMP (cAMP). However, its cardiac physiological function is unknown. On the other hand, the cardiac Na⁺/HCO₃⁻ cotransporter (NBC) promotes the cellular co-influx of HCO₃⁻ and Na⁺. Since sAC activity is regulated by HCO₃⁻, our purpose was to investigate the potential functional relationship between NBC and sAC in the cardiomyocyte. Rat ventricular myocytes were loaded with Fura-2, Fluo-3, or BCECF to measure Ca²⁺ transient (Ca²⁺i) by epifluorescence, Ca²⁺ sparks frequency (CaSF) by confocal microscopy, or intracellular pH (pHi) by epifluorescence, respectively. Sarcomere or cell shortening was measured with a video camera as an index of contractility. The NBC blocker S0859 (10 μM), the selective inhibitor of sAC KH7 (1 μM), and the PKA inhibitor H89 (0.1 μM) induced a negative inotropic effect which was associated with a decrease in Ca²⁺i. Since PKA increases Ca²⁺ release through sarcoplasmic reticulum RyR channels, CaSF was measured as an index of RyR open probability. The generation of CaSF was prevented by KH7. Finally, we investigated the potential role of sAC activation on NBC activity. NBC-mediated recovery from acidosis was faster in the presence of KH7 or H89, suggesting that the pathway sAC-PKA is negatively regulating NBC function, consistent with a negative feedback modulation of the HCO₃⁻ influx that activates sAC. In summary, the results demonstrated that the complex NBC-sAC-PKA plays a relevant role in Ca²⁺ handling and basal cardiac contractility.
format Articulo
Articulo
author Espejo, María Sofía
Orlowski, Alejandro
Ibañez, Alejandro Martín
Di Mattia, Romina Alejandra
Carrizo Velásquez, Fernanda Elisabeth
Rossetti, Noelia S.
Ciancio, María Carolina
De Giusti, Verónica Celeste
Aiello, Ernesto Alejandro
author_facet Espejo, María Sofía
Orlowski, Alejandro
Ibañez, Alejandro Martín
Di Mattia, Romina Alejandra
Carrizo Velásquez, Fernanda Elisabeth
Rossetti, Noelia S.
Ciancio, María Carolina
De Giusti, Verónica Celeste
Aiello, Ernesto Alejandro
author_sort Espejo, María Sofía
title The functional association between the sodium/bicarbonate cotransporter (NBC) and the soluble adenylyl cyclase (sAC) modulates cardiac contractility
title_short The functional association between the sodium/bicarbonate cotransporter (NBC) and the soluble adenylyl cyclase (sAC) modulates cardiac contractility
title_full The functional association between the sodium/bicarbonate cotransporter (NBC) and the soluble adenylyl cyclase (sAC) modulates cardiac contractility
title_fullStr The functional association between the sodium/bicarbonate cotransporter (NBC) and the soluble adenylyl cyclase (sAC) modulates cardiac contractility
title_full_unstemmed The functional association between the sodium/bicarbonate cotransporter (NBC) and the soluble adenylyl cyclase (sAC) modulates cardiac contractility
title_sort functional association between the sodium/bicarbonate cotransporter (nbc) and the soluble adenylyl cyclase (sac) modulates cardiac contractility
publishDate 2020
url http://sedici.unlp.edu.ar/handle/10915/138261
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