ß3-Adrenergic regulation of L-type Ca²âº current and force of contraction in human ventricle.
J Membr Biol
; 247(4): 309-18, 2014 Apr.
Article
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| MEDLINE
| ID: mdl-24531741
ß3-Adrenergic receptor (ß3-AR) is expressed in human atrial and ventricular tissues. Recently, we have demonstrated that it was involved in the activation of L-type Ca(2+) current (I(Ca,L)) in human atrial myocytes and the force of contraction of human atrial trabeculae. In the present study, we examined the effect of ß3-AR agonist CGP12177 which also is a ß1-AR/ß2-AR antagonist on I(Ca,L) in human ventricular myocytes (HVMs) and the force of contraction of human ventricular trabeculae. CGP12177 stimulated I(Ca,L) in HVMs with high potency but much lower efficacy than isoprenaline. The ß3-AR antagonist L-748,337 inhibited the effect of CGP12177. CGP12177 and L748,337 competed selectively on ß3-ARs because L748,337 had no effect on isoprenaline-induced stimulation of I(Ca,L), while CGP12177 completely blocked the effect of isoprenaline. The activation of ß3-ARs by CGP12177 does not involve the activation of Gi proteins because CGP12177 had no effect on forskolin-induced stimulation of I(Ca,L). CGP12177 had no effect on the force of contraction of human ventricular trabeculae. L-NMMA, an inhibitor of NO synthase, and IBMX, a nonselective inhibitor of phosphodiesterases, did not potentiate the effect of CGP12177 either on contraction of human ventricular trabeculae or on I(Ca,L) in HVMs. We conclude that in human ventricles ß3-AR activation has no inotropic effect, while it slightly increases I(Ca,L). In contrast to human atrium, the activation of ß3-ARs in human ventricle is not accompanied by increased activity of phosphodiesterases.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Señalización del Calcio
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Canales de Calcio Tipo L
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Receptores Adrenérgicos beta 3
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Contracción Miocárdica
Límite:
Adolescent
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Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Membr Biol
Año:
2014
Tipo del documento:
Article
País de afiliación:
Lituania
Pais de publicación:
Estados Unidos