{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T18:19:07Z","timestamp":1776277147419,"version":"3.50.1"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T00:00:00Z","timestamp":1751414400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T00:00:00Z","timestamp":1751414400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100025294","name":"Research Ireland","doi-asserted-by":"crossref","award":["21\/RC\/10294_P2"],"award-info":[{"award-number":["21\/RC\/10294_P2"]}],"id":[{"id":"10.13039\/501100025294","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100025294","name":"Research Ireland","doi-asserted-by":"crossref","award":["21\/RC\/10294_P2"],"award-info":[{"award-number":["21\/RC\/10294_P2"]}],"id":[{"id":"10.13039\/501100025294","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland","doi-asserted-by":"publisher","award":["17\/CDA\/4708"],"award-info":[{"award-number":["17\/CDA\/4708"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004593","name":"Universidad Aut\u00f3noma de Madrid","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004593","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Purinergic Signalling"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Epilepsy is one of the most common chronic brain diseases affecting up to 70 million people worldwide. Major challenges of epilepsy treatment include the high pharmacoresistance in patients and the lack of disease-modification. Extracellular adenosine 3\u2019triphosphate (ATP), a key neurotransmitter in the activation of the purinergic signalling system, is increasingly recognized to contribute to pathological brain hyperexcitability in epilepsy. Consequently, targeting ATP-release mechanisms may constitute a new therapeutic strategy for seizure control and epilepsy. The calcium channel, Calcium Homeostasis Modulator 1 (CALHM1), a voltage-gated, non-selective ion channel that permits the passage of various cations and small molecules, is expressed in neurons and plays an essential role during neuronal excitability and neurotransmission. In addition to ions, CALHM1 also allows the passage of ATP into the extracellular space, activating thereby purinergic receptors. Here, we tested if the pharmacological blocking of CALHM1 via CGP37157 (7-chloro-5-(2-chlorophenyl)-3,5-dihydro-4,1-benzothiazepin-2-(1H)-one) alters the severity of intra-amygdala kainic acid-induced status epilepticus. Our results show that CGP37157 increased the severity of seizures during status epilepticus. In addition, CALHM1 protein levels are down-regulated in the hippocampus in epileptic mice and Temporal Lobe Epilepsy (TLE) patients. In summary, our results identify CALHM1 as a new contributor to seizures and suggest targeting of CALHM1 as new treatment strategy for epilepsy.<\/jats:p>","DOI":"10.1007\/s11302-025-10103-9","type":"journal-article","created":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T00:55:17Z","timestamp":1751417717000},"page":"1241-1248","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The CALHM1 blocker CGP37157 increases seizure severity during status epilepticus in adult mice"],"prefix":"10.1007","volume":"21","author":[{"given":"Meghma","family":"Mitra","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amaya Sanz","family":"Rodriguez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norman","family":"Delanty","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan","family":"Beausang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca M.","family":"Brett","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael A.","family":"Farrell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jane","family":"Cryan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donncha F.","family":"O\u2019Brien","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Henshall","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria F.","family":"Cano-Abad","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tobias","family":"Engel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,7,2]]},"reference":[{"issue":"10172","key":"10103_CR1","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1016\/S0140-6736(18)32596-0","volume":"393","author":"RD Thijs","year":"2019","unstructured":"Thijs RD et al (2019) Epilepsy in adults. 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Prog Neurobiol 204:102105","journal-title":"Prog Neurobiol"},{"issue":"2","key":"10103_CR4","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1007\/s11302-016-9504-9","volume":"12","author":"F Dona","year":"2016","unstructured":"Dona F et al (2016) Variations of ATP and its metabolites in the hippocampus of rats subjected to pilocarpine-induced temporal lobe epilepsy. Purinergic Signal 12(2):295\u2013302","journal-title":"Purinergic Signal"},{"key":"10103_CR5","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.brainresbull.2018.12.021","volume":"151","author":"E Beamer","year":"2019","unstructured":"Beamer E et al (2019) ATP release during seizures - A critical evaluation of the evidence. 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