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Regulación dual de los canales de calcio dependientes de la tensión por medio de las PtdIns(4,5) P2P2
Li Wu1, Claudia S Bauer, Xiao-guang Zhen
1Department of Biological Sciences, Columbia University, New York, New York 10027, USA.
Nature
|November 1, 2002
Resumen
El fosfatidilinositol-4,5-bisfosfato (PtdIns(4,5) P2) es vital para los canales de calcio controlados por voltaje (VGCC) de tipo P/Q y N. Su hidrólisis inhibe los canales, pero la proteína quinasa A puede aliviar esto, permitiendo la regulación dinámica de los VGCC.
Área de la Ciencia:
- La neurociencia es la neurociencia.
- Biología celular Biología celular.
- La bioquímica es la bioquímica.
Sus antecedentes:
- Los canales de calcio regulados por voltaje (VGCC) son cruciales para la afluencia de calcio celular y los procesos biológicos.
- El resumen de la actividad de VGCC en las grabaciones sugiere una modulación intrínseca, con mecanismos para los canales de tipo L estudiados, pero otros poco comprendidos.
- El fosfatidilinositol-4,5-bisfosfato (PtdIns(4,5) P2) es un conocido regulador de canales iónicos.
Objetivo del estudio:
- Investigar el papel de los PtdIns{4,5) P2 en el mantenimiento de la actividad de los VGCC de tipo P/Q y N.
- Para dilucidar el mecanismo por el cual PtdIns(4,5) P2 modula la actividad del canal de tipo P/Q.
- Para explorar la interacción entre PtdIns{4,5) P2 y la proteína quinasa A en la regulación VGCC.
Principales métodos:
- Grabaciones de la pinza de parche de células enteras y de adentro hacia afuera en ovocitos y neuronas.
- Activación de los receptores de membrana para estimular la hidrólisis de las PtdIns.
- Investigando los efectos de PtdIns(4,5) P2 en la dependencia de la tensión del canal y la modulación por la fosforilación de la proteína quinasa A.
Principales resultados:
- PtdIns ((4,5) P2 es esencial para mantener la actividad de las VGCC de tipo P/Q y N.
- La estimulación de la hidrólisis de PtdIns ((4,5) P2 a través de los receptores de membrana inhibe estos canales.
- PtdIns{4,5) P2 inhibe directamente los canales de tipo P/Q al alterar la dependencia del voltaje de activación, un efecto invertido por la fosforilación de la proteína quinasa A.
Conclusiones:
- PtdIns{4,5) P2 juega un papel crítico en la regulación de los VGCC de tipo P/Q y N.
- La interacción dinámica entre PtdIns{4,5) P2 y la proteína quinasa A permite ajustar la actividad de VGCC.
- Este mecanismo permite la modulación de los VGCC por varias moléculas de señalización como los neurotransmisores y las hormonas.
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