Los canales de TRP permeables a los protones Ca2+ dañan la mielina en condiciones que imitan la isquemia
Nicola B Hamilton1, Karolina Kolodziejczyk1, Eleni Kougioumtzidou1
1Department of Neuroscience, Physiology &Pharmacology, University College London, Gower St., London WC1E 6BT, UK.
Nature
|January 14, 2016
Resumen
La isquemia daña la mielina en el cerebro, pero no a través de los receptores NMDA. En cambio, el aumento de la acidez intracelular activa los canales TRPA1, aumentando los niveles de calcio y dañando la mielina, lo que sugiere que TRPA1 es un objetivo terapéutico.
Área de la Ciencia:
- La neurociencia
- Biología celular
- La bioquímica
Sus antecedentes:
- Los oligodendrocitos producen vainas de mielina esenciales para la función cerebral.
- La isquemia causa daño a la mielina, deteriorando la propagación del potencial de acción.
- Este daño fue atribuido previamente a la activación del receptor de N-metil-D-aspartato (NMDA).
Objetivo del estudio:
- Investigar los mecanismos de daño de los oligodendrocitos durante la isquemia.
- Identificar los canales iónicos implicados en el aumento del calcio intracelular durante la isquemia.
- Para explorar posibles objetivos terapéuticos para la isquemia de la sustancia blanca.
Principales métodos:
- Electrofisiología para medir las corrientes de membrana y las concentraciones de iones intracelulares ([Ca2+]i, [Mg2+]i, [H2+]i).
- Inhibición farmacológica y eliminación genética de los canales TRPA1.
- Evaluación del daño de la mielina en condiciones isquémicas con y sin inhibición de TRPA1.
Principales resultados:
- La NMDA no aumentó el calcio intracelular en los oligodendrocitos maduros durante la isquemia.
- La isquemia indujo una corriente desencadenada por el glutamato a través del aumento del potasio extracelular y la disminución de la conductividad del potasio.
- La acidosis intracelular (aumento en [H(+) i) desencadenó la afluencia de calcio y magnesio a través de los canales TRPA1, lo que condujo al daño de la mielina.
- La inhibición del canal TRPA1 redujo el daño de la mielina en la isquemia.
Conclusiones:
- El mecanismo de daño de los oligodendrocitos en la isquemia implica la acidosis intracelular que activa los canales TRPA1, no los receptores NMDA.
- Los canales TRPA1 son mediadores clave de la afluencia de calcio y magnesio durante la isquemia de la sustancia blanca.
- Los canales iónicos que contienen TRPA1 representan un objetivo terapéutico prometedor para el tratamiento de la isquemia de la sustancia blanca.
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