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Regulación defectuosa del receptor cardíaco de la ryanodina durante la fibrilación auricular
John A Vest1, Xander H T Wehrens, Steven R Reiken
1Department of Physiology and Cellular Biophysics, Clyde and Helen Wu Center for Molecular Cardiology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Circulation
|April 27, 2005
Resumen
La fuga de calcio (Ca2+) del retículo sarcoplásmico desde el receptor cardíaco de ryanodina 2 (RyR2) debido a la hiperfosforilación de la proteína quinasa A (PKA) puede contribuir a la fibrilación auricular (FA). Esta disfunción de RyR2 y la reducción de la unión a calstabin2 se observaron tanto en modelos caninos como humanos de AF.
Área de la Ciencia:
- Investigaciones Cardiovasculares Investigación Cardiovascular Investigaciones Cardiovasculares
- Cardiología Molecular Cardiología Molecular
- Mecanismos de las arritmias.
Sus antecedentes:
- La fuga de calcio (Ca2+) del retículo sarcoplásmico (SR) está implicada en las arritmias auriculares como la fibrilación auricular (FA).
- La hiperfosforilación de la proteína quinasa A (PKA) del receptor cardíaco de la ryanodina (RyR2) puede causar fugas de SR Ca2+ y arritmias ventriculares, pero su papel en la FA no está claro.
Objetivo del estudio:
- Para investigar el papel de la disfunción de RyR2 en la fibrilación auricular (FA).
- Examinar la fosforilación por PKA de RyR2 y su asociación con la unión de calstabin2 en AF.
Principales métodos:
- Se recolectó tejido auricular de perros y humanos con FA y controles.
- Se evaluó la fosforilación por PKA de la unión de RyR2 y calstabin2 utilizando inmunoprecipitación e inmunoblotación.
- Se midieron las corrientes de los canales RyR2 en bicapas lipídicas planas.
Principales resultados:
- El tejido auricular tanto de perros AF como de humanos mostró un aumento de la fosforilación PKA de RyR2 y una disminución de la unión a calstabin2.
- Los canales RyR2 de los perros AF exhibieron una mayor probabilidad de apertura durante la diástole, lo que sugiere la posibilidad de una fuga de Ca2+ SR.
- Estos hallazgos indican una disfunción del canal RyR2 en la AF.
Conclusiones:
- La fuga de SR Ca2+ mediada por la hiperfosforilación de RyR2 PKA puede contribuir al inicio y mantenimiento de la FA.
- La disfunción de RyR2 es un mecanismo potencial subyacente a la fibrilación auricular.
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