{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T14:57:22Z","timestamp":1775141842981,"version":"3.50.1"},"reference-count":50,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2021,9,23]],"date-time":"2021-09-23T00:00:00Z","timestamp":1632355200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Lamotrigine and other sodium\u2010channel blocking agents are among the most commonly used antiepileptic drugs (AEDs). Because other sodium channel blockers, such as riluzole, can severely alter respiratory rhythm generation during hypoxia, we wanted to investigate if AEDs can have similar effects. This is especially important in the context of sudden unexpected death in epilepsy (SUDEP), the major cause of death in patients suffering from therapy\u2010resistant epilepsy. Although the mechanism of action is not entirely understood, respiratory dysfunction after generalized tonic\u2010clonic seizures seems to play a major role.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used transverse brainstem slice preparations from neonatal and juvenile mice containing the pre\u2010B\u00f6tzinger complex (PreB\u00f6tC) and measured population as well as intracellular activity of the rhythm\u2010generating network under normoxia and hypoxia in the presence or absence of AEDs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found a substantial inhibition of the gasping response induced by the application of sodium channel blockers (lamotrigine and carbamazepine). In contrast, levetiracetam, an AED\u2010modulating synaptic function, had a much smaller effect. The inhibition of gasping by lamotrigine was accompanied by a significant reduction of the persistent sodium current (INap) in PreB\u00f6tC neurons. Surprisingly, the suppression of persistent sodium currents by lamotrigine did not affect the voltage\u2010dependent bursting activity in PreB\u00f6tC pacemaker neurons, but led to a hypoxia\u2010dependent shift of the action potential rheobase in all measured PreB\u00f6tC neurons.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Our results contribute to the understanding of the effects of AEDs on the vital respiratory functions of the central nervous system. Moreover, our study adds further insight into sodium\u2010dependent changes occurring during hypoxia and the contribution of cellular properties to the respiratory rhythm generation in the pre\u2010B\u00f6tzinger complex. It raises the question of whether sodium channel blocking AEDs could, in conditions of extreme hypoxia, contribute to SUDEP, an important issue that warrants further studies.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.17066","type":"journal-article","created":{"date-parts":[[2021,9,23]],"date-time":"2021-09-23T09:16:03Z","timestamp":1632388563000},"page":"2790-2803","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The effect of lamotrigine and other antiepileptic drugs on respiratory rhythm generation in the pre\u2010B\u00f6tzinger complex"],"prefix":"10.1111","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1369-2240","authenticated-orcid":false,"given":"Nikolas","family":"Layer","sequence":"first","affiliation":[{"name":"Department of Neurology and Epileptology Hertie\u2010Institute for Clinical Brain Research University of T\u00fcbingen T\u00fcbingen 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