Cardiac function and electrical remodeling of the calcineurin-overexpressed transgenic mouse.
Cardiovasc Res
; 54(1): 117-32, 2002 Apr.
Article
en En
| MEDLINE
| ID: mdl-12062368
ABSTRACT
OBJECTIVE:
To study the specificity of contractile phenotype and electrophysiological remodeling in transgenic (Tg) mice with cardiac directed calcineurin (phosphatase 2B) overexpression and evaluate a possible negative role of chronically activated calcineurin in beta-adrenergic mediated contractile response.METHODS:
The patch-clamp technique was used to characterize electrophysiological properties of action potentials and inward rectifier (I(K1)), and transient outward potassium currents (I(to)). The analysis of the contractile performance was carried out on isolated retrograde perfused hearts at constant aortic pressure.RESULTS:
Tg mice demonstrated a hypercontractile phenotype characterized by a profound beta-adrenergic hypo-responsiveness at 2.0 mM [Ca2+](o). Transgenic cardiomyocytes showed marked action potential prolongation (209% in APD(90)) with increased I(to,peak) and I(sus) and decreased protein expression level of Kv1.5 and Kv2.1. Lowering [Ca2+](o) to 0.75 mM restored the beta-adrenergic response, indicating that the calcineurin/calmodulin/adenylyl cyclase (AC) pathway may not be directly responsible for the blunted beta-adrenoreceptor mediated inotropism.CONCLUSIONS:
Calcineurin overexpression leads to development of a hyperdynamic phenotype with a cellular profile of increased calcium influx. This type of functional hypertrophic remodeling is accompanied by a negative feedback regulation between increased calcium handling and beta-adrenergic contractile activation.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Potenciales de Acción
/
Canales de Potasio
/
Cardiomegalia
/
Calcineurina
/
Contracción Miocárdica
Límite:
Animals
Idioma:
En
Revista:
Cardiovasc Res
Año:
2002
Tipo del documento:
Article
País de afiliación:
Estados Unidos