Oxidation of KCNB1 Potassium Channels Causes Neurotoxicity and Cognitive Impairment in a Mouse Model of Traumatic Brain Injury.

Abstract

This study provides the first experimental evidence that oxidation of a K+ channel constitutes a mechanism of neuronal and cognitive impairment in vertebrates. Specifically, the interaction of KCNB1 channels with reactive oxygen species plays a major role in the etiology of mouse model of traumatic brain injury (TBI), a condition associated with extensive oxidative stress. In addition, a Food and Drug Administration-approved drug ameliorates the outcome of TBI in mouse, by directly impinging on the toxic pathway activated in response to oxidation of the KCNB1 channel. These findings elucidate a basic mechanism of neurotoxicity in vertebrates and might lead to a new therapeutic approach to TBI in humans, which, despite significant efforts, is a condition that remains without effective pharmacological treatments.