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Consecuencias bioenergéticas adversas de la afluencia de Ca2+ mediada por el intercambiador Na+-Ca2+ en los miocitos
Michael Kohlhaas1, Christoph Maack
1Universitätsklinikum des Saarlandes, Klinik für Innere Medizin III, 66421 Homburg, Germany.
Circulation
|November 25, 2010
Resumen
En la insuficiencia cardíaca, el intercambiador de sodio y calcio (NCX) afecta la absorción de calcio mitocondrial, lo que puede causar hambre de energía en los corazones con insuficiencia. Esto afecta la producción de energía celular y la función cardíaca.
Área de la Ciencia:
- Cardiología Cardiología.
- Fisiología Celular Fisiología celular
- Biología mitocondrial Biología mitocondrial
Sus antecedentes:
- En la insuficiencia cardíaca, el intercambiador de sodio y calcio (NCX) está regulado al alza, mediando la afluencia de calcio.
- Esta actividad NCX puede tener consecuencias energéticas no consideradas.
- La absorción de calcio mitocondrial, crucial para la producción de energía, se basa en los gradientes de calcio.
Objetivo del estudio:
- Para investigar el impacto de la afluencia de calcio mediada por NCX en la bioenergética mitocondrial.
- Para determinar si la actividad de NCX afecta la eficiencia de la absorción de calcio mitocondrial y la actividad del ciclo de Krebs.
Principales métodos:
- Utilizó una técnica de pinza de parche en los miocitos de cobayas para medir el calcio citosólico y mitocondrial.
- Variada afluencia de calcio a través de los canales de calcio de tipo L (I(Ca,L)) y NCX.
- Evalúa la eficiencia de la absorción de calcio mitocondrial trazando el calcio mitocondrial frente al citosólico durante los transitorios.
Principales resultados:
- La eficiencia de la absorción de calcio mitocondrial fue máxima durante la liberación de calcio desencadenada por I ((Ca,L).
- La reducción de la carga de calcio en el retículo sarcoplásmico y el aumento de la actividad de la NCX disminuyeron la eficiencia de la absorción de calcio mitocondrial.
- La velocidad ascendente transitoria del calcio citosólico se correlacionó con la eficiencia de la absorción de calcio mitocondrial.
- La afluencia de calcio mediada por NCX no estimuló las deshidrogenasas del ciclo de Krebs, a diferencia de la liberación del retículo sarcoplásmico.
Conclusiones:
- El aumento de la contribución de NCX a los transitorios de calcio citosólico en la insuficiencia cardíaca afecta la absorción de calcio mitocondrial.
- Esta absorción deteriorada afecta negativamente la respuesta de retroalimentación bioenergética.
- El mecanismo puede contribuir al hambre de energía observada en los corazones con insuficiencia cardíaca.
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