TREK-1 and epilepsy: regulating the balance of K+ and the glutamate release in astrocyte-neuron interactions.

Abstract

The TWIK-related K⁺ channel (TREK-1), a member of the two-pore domain potassium(K2P) family, is characterized as a "leaky potassium channel" and is integral to the maintenance of the resting membrane potential. As the most abundant cell type in the central nervous system, astrocytes play important roles in the development of epilepsy by regulating the release of glutamate and the function of potassium channels. Previous studies have revealed that TREK-1 is involved in a range of neurological diseases, including epilepsy. In astrocytes, TREK-1 acts as a crucial regulator of the rapid release of glutamate and passive conductance. However, controversy remains about the expression levels of TREK-1-binding receptors in the process of the release and recycling of glutamate in tripartite synapses. Thus, elucidating the pathological mechanisms involving TREK-1 in epilepsy could significantly increase our understanding of the pathophysiological basis of diseases and facilitate the identification of potential targets for novel therapeutic interventions. Here, we review the physiological function of TREK-1 and studies examining the role of TREK-1 in epilepsy, with a particular emphasis on its interactions with glutamate at tripartite synapses. Furthermore, we provide an analysis of the associated molecular mechanisms of this channel and conclude with an outlook on impending studies on TREK-1 as a novel therapeutic target for epilepsy.