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Potassium channel subfamily K member 18 (KCNK18)
- Target
- KCNK18
- Molecular classification
- Ion channel, Two-pore domain potassium channel (K2P channel), Membrane protein
01
Overview
Potassium channel subfamily K member 18 (KCNK18, also known as TRESK or K2P18.1) is a membrane protein that forms a two-pore domain, background potassium channel in the K2P family. It conducts outward and inward rectifying potassium currents and regulates the resting membrane potential, particularly in sensory neurons of the trigeminal ganglia, where it modulates neuronal firing threshold, frequency, and neurogenic inflammation. Mutations in KCNK18 are linked to migraine susceptibility through increased sensitivity of pain pathways, making it a potential therapeutic target for migraine and other pain syndromes[1][2][3][7].
- Other names
- KCNK18K2P18.1TRESKTRESK-2TRESK2TRIKMGR13TWIK-related spinal cord potassium channelpotassium two-pore domain channel subfamily K member 18potassium two pore domain channel subfamily K member 18
02
Mechanism of action
Channel activators enhance K+ current and stabilize membrane potential (e.g., via calcium/calcineurin pathway); Channel blockers inhibit K+ current and increase neuronal excitability (e.g., free fatty acids, acidic pH)
03
Biological functions
Regulation of resting membrane potentialModulation of neuronal excitabilityInhibition of neuronal firing and neurogenic inflammationBackground potassium conductance
04
Disease associations
Migraine (mutations in KCNK18 can trigger migraine headaches)Neuropathic pain/sensory neuron excitability modulationOther neurogenic or pain-related conditions (inferred from function)
05
Safety considerations
Potential for altered neuronal excitability leading to headache, migraine, or pain disorders if modulated inappropriatelyOff-target effects due to broad role in resting membrane potentialLimited clinical experience with selective TRESK modulators, so safety profile is not well established
06
Interacting drugs
Free fatty acids (blocker)
3 more in the full profile.
07
Biomarkers
Mutations in KCNK18 gene as a genetic biomarker for migraine susceptibilityNo established circulating or molecular biomarkers for efficacy monitoring (as of current knowledge)
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