ArticleJournal of neurophysiology2014
Nonmigraine-associated TRESK K+ channel variant C110R does not increase the excitability of trigeminal ganglion neurons.
Article in Journal of neurophysiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 30 citations in OpenAlex.
- Migraine is a dysfunction of neuronal potassium ion channels.Frontiers in neurology · 2025Review
- Genetic Mechanisms of Migraine: Insights from Monogenic Migraine Mutations.International journal of molecular sciences · 2023Review
- Study of variants in genes implicated in rare familial migraine syndromes and their association with migraine in 200,000 exome-sequenced UK Biobank participants.Annals of human genetics · 2022Article
- TREK channel activation suppresses migraine pain phenotype.iScience · 2021Article
- TRESK and TREK-2 two-pore-domain potassium channel subunits form functional heterodimers in primary somatosensory neurons.The Journal of biological chemistry · 2020Article
- The Background KInternational journal of molecular sciences · 2020Review
- Genetics of migraine aura: an update.The journal of headache and pain · 2020Review
- A causal role for TRESK loss of function in migraine mechanisms.Brain : a journal of neurology · 2019Article
- Evolution of acid nociception: ion channels and receptors for detecting acid.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2019Review
- Advances in genetics of migraine.The journal of headache and pain · 2019Review
- Verapamil Inhibits TRESK (KInternational journal of molecular sciences · 2018Article
- Ion channelopathies and migraine pathogenesis.Molecular genetics and genomics : MGG · 2017Review
- Dominant-Negative Effect of a Missense Variant in the TASK-2 (KCNK5) K+ Channel Associated with Balkan Endemic Nephropathy.PloS one · 2016Article
- Two-pore domain potassium channels: potential therapeutic targets for the treatment of pain.Pflugers Archiv : European journal of physiology · 2015Review
- Properties, regulation, pharmacology, and functions of the K₂p channel, TRESK.Pflugers Archiv : European journal of physiology · 2015Review
- Molecular aspects of structure, gating, and physiology of pH-sensitive background K2P and Kir K+-transport channels.Physiological reviews · 2015Review
- TRESK KeNeuroArticle
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Recent genetic studies suggest that dysfunction of ion channels and transporters may contribute to migraine pathophysiology. A migraine-associated frameshift mutation in the TWIK-related spinal cord K+ (TRESK) channel results in nonfunctional channels. Moreover, mutant TRESK subunits exert a dominant-negative effect on whole cell TRESK currents and result in hyperexcitability of small-diameter trigeminal ganglion (TG) neurons, suggesting that mutant TRESK may increase the gain of the neuronal circuit underlying migraine headache. However, the nonmigraine-associated TRESK C110R variant exhibits the same effect on TRESK currents as the mutant subunits in Xenopus oocytes, suggesting that dysfunction of TRESK is not sufficient to cause migraine. Here, we confirmed that the C110R variant formed nonfunctional channels and exerted a dominant-negative effect on TRESK currents in HEK293T cells, similar to the migraine-associated mutant TRESK. To compare the functional consequences of TRESK mutations/variants in a more physiological setting, we expressed the mutant TRESK and the C110R variant in cultured mouse TG neurons and investigated their effects on background K+ currents and neuronal excitability. Both mutant TRESK and the C110R variant reduced the endogenous TRESK currents in TG neurons, but the effect of the C110R variant was significantly smaller. Importantly, only TG neurons expressing mutant TRESK subunits, but not those expressing the C110R variant, exhibited a significant increase in excitability. Thus only the migraine-associated TRESK mutation, but not the C110R variant, reduces the endogenous TRESK currents to a degree that affects TG excitability. Our results support a potential causal relationship between the frameshift TRESK mutation and migraine susceptibility.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.