ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
Functional analysis of a migraine-associated TRESK K+ channel mutation.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.
- Mechanosensitive receptors in migraine: a systematic review.The journal of headache and pain · 2024Pooled it
- Migraine is a dysfunction of neuronal potassium ion channels.Frontiers in neurology · 2025Review
- Alterations in DNA methylation associate with reduced migraine and headache days after medication withdrawal treatment in chronic migraine patients: a longitudinal study.Clinical epigenetics · 2023Article
- 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
- Peripheral Ion Channel Gene Screening in Painful- and Painless-Diabetic Neuropathy.International journal of molecular sciences · 2022Article
- Block of TREK and TRESK K2P channels by lamotrigine and two derivatives sipatrigine and CEN-092.Biochemistry and biophysics reports · 2021Article
- Common variants in KCNK5 and FHL5 genes contributed to the susceptibility of migraine without aura in Han Chinese population.Scientific reports · 2021Article
- Contribution of Neuronal and Glial Two-Pore-Domain Potassium Channels in Health and Neurological Disorders.Neural plasticity · 2021Review
- Ion Channel Dysfunction and Neuroinflammation in Migraine and Depression.Frontiers in pharmacology · 2021Review
- Exploring the Hereditary Nature of Migraine.Neuropsychiatric disease and treatment · 2021Review
- 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
- Analysis of Genetic Variants inCurrent genomics · 2020Article
- 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
- Anionic Phospholipids Bind to and Modulate the Activity of Human TRESK Background KMolecular neurobiology · 2019Article
- Two-pore domain potassium channels: emerging targets for novel analgesic drugs: IUPHAR Review 26.British journal of pharmacology · 2019Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Recent genetic and functional studies suggest that migraine may result from abnormal activities of ion channels and transporters. A frameshift mutation in the human TWIK-related spinal cord K(+) (TRESK) channel has been identified in migraine with aura patients in a large pedigree. In Xenopus oocytes, mutant TRESK subunits exert a dominant-negative effect on whole-cell TRESK currents. However, questions remain as to whether and how mutant TRESK subunits affect the membrane properties and the excitability of neurons in the migraine circuit. Here, we investigated the functional consequences of the mutant TRESK subunits in HEK293T cells and mouse trigeminal ganglion (TG) neurons. First, we found that mutant TRESK subunits exhibited dominant-negative effects not only on the size of the whole-cell TRESK currents, but also on the level of TRESK channels on the plasma membrane in HEK293T cells. This likely resulted from the heterodimerization of wild-type and mutant TRESK subunits. Next, we expressed mutant TRESK subunits in cultured TG neurons and observed a significant decrease in the lamotrigine-sensitive K(+) current, suggesting that the mutant TRESK subunits have a dominant-negative effect on currents through the endogenous TRESK channels. Current-clamp recordings showed that neurons expressing mutant TRESK subunits had a higher input resistance, a lower current threshold for action potential initiation, and a higher spike frequency in response to suprathreshold stimuli, indicating that the mutation resulted in hyperexcitability of TG neurons. Our results suggest a possible mechanism through which the TRESK mutation increases the susceptibility of migraine headache.
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