The Background K+ Channel TRESK in Sensory Physiology and Pain

Abstract

TRESK belongs to the K2P family of potassium channels, also known as background or leak potassium channels due to their biophysical properties and their role regulating membrane potential of cells. Several studies to date have highlighted the role of TRESK in regulating the excitability of specific subtypes of sensory neurons. These findings suggest TRESK could be involved in pain sensitivity. Here, we review the different evidence available that involves the channel in pain and sensory perception, from studies knocking out the channel or overexpressing it to identified mutations that link the channel to migraine pain. In addition, the therapeutic possibilities are discussed, as targeting the channel seems an interesting therapeutic approach to reduce nociceptor activation and to decrease pain.

Potassium Ion Channel Protein (KCNH) Levels in Patients with Fibromyalgia Syndrome

“…Kv is one of the bestdocumented channels. K + channels participate in numerous cellular functions (20). As Kv channels function in many various cellular events, there is an increasing number of studies that have investigated the function of the K + ion channel in different disease groups, primarily cancer and cardiac diseases (21,22).…”

Flavonoids as Modulators of Potassium Channels

“…They are emerging drug targets in case of a.o. cardiovascular and neurological diseases [ 187 , 188 , 189 , 190 ]. The K2P channels are a family of 15 channel subtypes, including the TWIK channels (named as an acronym for Tandem of pore domains in a Weak Inward rectifying channels) , and , TREK channels (TWIK-related channels): and , TRAAK channel (TWIK-related arachidonic acid-activated potassium channel) belonging to the TREK subgroup: , TASK channels (TWIK-related acid-sensitive channel channels): , , and , THIK channels (tandem pore domain halothane-inhibited channels): and , TALK channels (TWIK-related alkaline pH-activated channels): and , and TRIK channel (TWIK-related spinal cord channel) …”

What Is the Role of 2-Pore Domain Potassium Channels (K2P) in Pain?

“…49,81,82 Several studies indicate a major role of TRESK in regulation of excitability of nociceptive neurons. [17][18][19] For example, TRESK activation reduced TRPV1-induced responses in DRG neurons and decreased release of the Glossary DRG = dorsal root ganglion; PKA = protein kinase A; PKC = protein kinase C; TALK = TWIK-related alkaline pH-activated K + channel; TASK = TWIK-related acid-sensitive K + channel; THIK = tandem pore domain halothane-inhibited K + channel; TRAAK = TWIK-related arachidonic acid-sensitive K + channel; TREK = TWIK-related K + channel; TRESK = TWIK-related spinal cord K + channel; TRP = transient receptor potential; TWIK = tandem of pore domains in weak inward rectifying K + channel. calcitonin gene-related peptide from trigeminal afferents.…”

“…49,81,82 Several studies indicate a major role of TRESK in regulation of excitability of nociceptive neurons. 17-19 For example, TRESK activation reduced TRPV1-induced responses in DRG neurons and decreased release of the calcitonin gene-related peptide from trigeminal afferents. 83 In cultured trigeminal ganglion neurons, TRESK overexpression increased total background K + currents and threshold for action potential initiation, reduced spike frequency, and inhibited capsaicin-evoked spikes.…”