{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T14:16:56Z","timestamp":1789827416797,"version":"4.0.1"},"reference-count":49,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,11,24]],"date-time":"2018-11-24T00:00:00Z","timestamp":1543017600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Deutsche RLS Vereinigung"},{"name":"Medical School Goettingen"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Restless legs patients complain about sensory and motor symptoms leading to sleep disturbances. Symptoms include painful sensations, an urge to move and involuntary leg movements.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The responsible mechanisms of restless legs syndrome are still not known, although current studies indicate an increased neuronal network excitability. Reflex studies indicate the involvement of spinal structures. Peripheral mechanisms have not been investigated so far.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In the present study, we provide evidence of increased hyperpolarization\u2010activated cyclic nucleotide\u2010gated (HCN) channel\u2010mediated inward rectification in motor axons. The excitability of sensory axons was not changed.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We conclude that, in restless legs syndrome, an increased HCN current in motoneurons may play a pathophysiological role, such that these channels could represent a valuable target for pharmaceutical intervention.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Restless legs syndrome is a sensorimotor network disorder. So far, the responsible pathophysiological mechanisms are poorly understood. In the present study, we provide evidence that the excitability of peripheral motoneurons contributes to the pathophysiology of restless legs syndrome. <jats:italic>In vivo<\/jats:italic> excitability studies on motor and sensory axons of the median nerve were performed on patients with idiopathic restless legs syndrome (iRLS) who were not currently on treatment. The iRLS patients had greater accommodation in motor but not sensory axons to long\u2010lasting hyperpolarization compared to age\u2010matched healthy subjects, indicating greater inward rectification in iRLS. The most reasonable explanation is that hyperpolarization\u2010activated cyclic nucleotide\u2010gated (HCN) channels open at less hyperpolarized membrane potentials, a view supported by mathematical modelling. The half\u2010activation potential for HCN channels (Bq) was the single best parameter that accounted for the difference between normal controls and iRLS data. A 6\u00a0mV depolarization of Bq reduced the discrepancy between the normal control model and the iRLS data by 92.1%. Taken together, our results suggest an increase in the excitability of motor units in iRLS that could enhance the likelihood of leg movements. The abnormal axonal properties are consistent with other findings indicating that the peripheral system is part of the network involved in iRLS.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp275341","type":"journal-article","created":{"date-parts":[[2018,11,15]],"date-time":"2018-11-15T05:18:07Z","timestamp":1542259087000},"page":"599-609","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["<i>I<\/i><sub>h<\/sub> contributes to increased motoneuron excitability in restless legs syndrome"],"prefix":"10.1113","volume":"597","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2909-359X","authenticated-orcid":false,"given":"Dirk","family":"Czesnik","sequence":"first","affiliation":[{"name":"Department of Clinical Neurophysiology Medical School G\u00f6ttingen University of G\u00f6ttingen  G\u00f6ttingen 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