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Movimiento de carga durante la translocación de Na+ por intercambiadores cardíacos Na+/Ca2+ nativos y clonados
D W Hilgemann1, D A Nicoll, K D Philipson
1Department of Physiology, University of Texas Southwestern Medical Center, Dallas 75235.
Nature
|August 22, 1991
Resumen
El intercambiador cardíaco de sodio y calcio (NCX) mueve la carga positiva durante el transporte de sodio (Na+). Este estudio revela la naturaleza electrogénica del movimiento de Na+ en los miocitos cardíacos, aclarando el ciclo de reacción NCX.
Área de la Ciencia:
- La biofísica es la biofísica.
- Fisiología cardiovascular fisiología cardiovascular.
Sus antecedentes:
- El intercambiador cardíaco de sodio y calcio (NCX) juega un papel crucial en la regulación de los niveles de calcio intracelular en las células del corazón.
- La naturaleza electrogénica y el ciclo de reacción detallado del NCX no se comprenden completamente, en particular la estequiometría del transporte de iones.
Objetivo del estudio:
- Investigar las propiedades electrogénicas de la translocación de Na+ por el NCX cardíaco.
- Para aclarar los detalles del ciclo de reacción NCX asociando el movimiento de carga con el transporte de Na+.
Principales métodos:
- Utilizó parches de membrana gigante de miocitos cardíacos y ovocitos que expresan el NCX cardíaco clonado.
- Los movimientos de carga inducidos por Na (((+) medidos en respuesta a incrementos escalonados de la concentración de Na+ en el citoplasma en ausencia de Ca2+.
- Densidades y tasas de volumen de negocios cuantificadas de la corriente de cambio de estado estacionario Na+/Ca2+ (INaCa).
Principales resultados:
- La translocación demostrada de Na+ por el NCX cardíaco está asociada con el movimiento de carga positiva.
- Se estima aproximadamente 400 intercambiadores por micrón cuadrado en el sarcolema de conejillo de indias y tasas de rotación máximas de 5,000 s-1.
- Se observó un aumento de las afinidades aparentes de iones con disminución de las concentraciones de contraiones y pérdida de dependencia de voltaje con disminución de la concentración de Ca2+, lo que apoya una translocación electroneutral de Ca2+.
Conclusiones:
- El paso electrogénico principal en el ciclo NCX parece ocurrir en el extremo extracelular de la vía de translocación de Na+.
- Los hallazgos proporcionan información sobre el mecanismo de reacción y la estequiometría del NCX cardíaco.
- El estudio aclara el comportamiento electrofisiológico del intercambiador cardíaco de sodio y calcio.
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