The Special One: Architecture, Physiology and Pharmacology of the TRESK Channel.

The TWIK-related spinal cord K channel (TRESK) is part of the two-pore domain K channel family (K), which are also called leak potassium channels. As indicated by the channel family name, TRESK conducts K ions along the concentration gradient in a nearly voltage-independent manner leading to lowered membrane potentials. Although functional and pharmacological similarities exist, TRESK shows low sequence identity with other K channels. Moreover, the channel possesses several unique features such as its sensitivity to intracellular Ca ions, that are not found in other K2P channels. High expression rates are found in immune-associated and neuronal cells, especially in sensory neurons of the dorsal root and trigeminal ganglia. As a consequence of the induced hyperpolarization, TRESK influences neuronal firing, the release of inflammatory mediators and the proliferation of distinct immune cells. Consequently, this channel might be a suitable target for pharmacological intervention in migraine, epilepsy, neuropathic pain or distinct immune diseases. In this review, we summarize the biochemical and biophysical properties of TRESK channels as well as their sensitivity to different known compounds. Furthermore, we give a structured overview about the physiological and pathophysiological impact of TRESK, that render the channel as an interesting target for specific drug development.