Caveolin-3 regulates compartmentation of cardiomyocyte beta2-adrenergic receptor-mediated cAMP signaling.
J Mol Cell Cardiol
; 67: 38-48, 2014 Feb.
Article
en En
| MEDLINE
| ID: mdl-24345421
ABSTRACT
The purpose of this study was to investigate whether caveolin-3 (Cav3) regulates localization of ß2-adrenergic receptor (ß2AR) and its cAMP signaling in healthy or failing cardiomyocytes. We co-expressed wildtype Cav3 or its dominant-negative mutant (Cav3DN) together with the Förster resonance energy transfer (FRET)-based cAMP sensor Epac2-camps in adult rat ventricular myocytes (ARVMs). FRET and scanning ion conductance microscopy were used to locally stimulate ß2AR and to measure cytosolic cAMP. Cav3 overexpression increased the number of caveolae and decreased the magnitude of ß2AR-cAMP signal. Conversely, Cav3DN expression resulted in an increased ß2AR-cAMP response without altering the whole-cell L-type calcium current. Following local stimulation of Cav3DN-expressing ARVMs, ß2AR response could only be generated in T-tubules. However, the normally compartmentalized ß2AR-cAMP signal became diffuse, similar to the situation observed in heart failure. Finally, overexpression of Cav3 in failing myocytes led to partial ß2AR redistribution back into the T-tubules. In conclusion, Cav3 plays a crucial role for the localization of ß2AR and compartmentation of ß2AR-cAMP signaling to the T-tubules of healthy ARVMs, and overexpression of Cav3 in failing myocytes can partially restore the disrupted localization of these receptors.
Palabras clave
ARVM; Beta-adrenergic receptors; Cardiomyocytes; Cav3; Cav3DN; FRET; HF; MßCD; SICM; T-tubules; adult rat ventricular myocytes; caveolin-3; caveolin-3 dominant negative mutant; fluorescence resonance energy transfer; heart failure; methyl-ß-cyclodextrin; scanning ion conductance microscopy; ß-AR; ß-adrenergic receptor
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Simulación por Computador
/
Transducción de Señal
/
Receptores Adrenérgicos beta 2
/
AMP Cíclico
/
Miocitos Cardíacos
/
Caveolina 3
Límite:
Animals
Idioma:
En
Revista:
J Mol Cell Cardiol
Año:
2014
Tipo del documento:
Article
País de afiliación:
Reino Unido