N-Methyl-d-aspartate Receptor- and Calpain-mediated Proteolytic Cleavage of K+-Cl−Cotransporter-2 Impairs Spinal Chloride Homeostasis in Neuropathic Pain
作者： Hong-Yi Zhou , Shao-Rui Chen , Hee-Sun Byun , Hong Chen , Li Li
关键词:
摘要: Loss of synaptic inhibition by γ-aminobutyric acid and glycine due to potassium chloride cotransporter-2 (KCC2) down-regulation in the spinal cord is a critical mechanism plasticity neuropathic pain. Here we present novel evidence that peripheral nerve injury diminishes glycine-mediated induces depolarizing shift reversal potential currents (Eglycine) dorsal horn neurons. Blocking glutamate N-methyl-d-aspartate (NMDA) receptors normalizes inhibition, Eglycine, KCC2 injury. Strikingly, increases calcium-dependent calpain activity turn causes cleavage at C terminus. Inhibiting blocks induced NMDA, thereby normalizing Eglycine. Furthermore, or silencing μ-calpain level reduces Thus, promotes proteolytic through NMDA receptor-calpain activation, resulting disruption homeostasis diminished cord. Targeting may represent new strategy for restoring levels tonic treating chronic
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