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Patients with SCA42 exhibit a pure form of cerebellar ataxia. We encountered a patient with the p.Arg1715His mutation, suffering from intractable resting tremor, particularly head tremor. This symptom improved with the administration of low-dose of zonisamide (ZNS), a T-type calcium channel blocker effective for treating Parkinson\u2019s disease and epilepsy. Previous electrophysiological studies showed that the voltage dependence of this mutant Ca<jats:sub>V<\/jats:sub>3.1 was shifted toward the positive potential. This abnormal shift was considered a factor related to disease onset and symptoms. In this study, we performed whole-cell recordings of GFP-expressing HEK293T cells that expressed wild-type or mutant Ca<jats:sub>V<\/jats:sub>3.1 and investigated the changes in the abnormal shift of voltage dependence of the mutant Ca<jats:sub>V<\/jats:sub>3.1. The results showed that ZNS in an amount equivalent to the patient\u2019s internal dose significantly ameliorated the abnormal shift in the mutant Ca<jats:sub>V<\/jats:sub>3.1, giving values close to those in the wild-type. On the other hand, ZNS did not affect the voltage dependence of wild-type Ca<jats:sub>V<\/jats:sub>3.1. Because Ca<jats:sub>V<\/jats:sub>3.1 is known to be involved in tremogenesis, modulation of the voltage dependence of mutant Ca<jats:sub>V<\/jats:sub>3.1 by ZNS might have contributed to improvement in the intractable tremor of our patient with SCA42. Moreover, efonidipine, another T-type calcium channel blocker, had no effect on tremors in our patient with SCA42 and did not improve the abnormal shift in the voltage dependence of the mutant Ca<jats:sub>V<\/jats:sub>3.1. This indicates that ZNS is distinct from other T-type calcium channel blockers in terms of modulation of the voltage dependence of the mutant Ca<jats:sub>V<\/jats:sub>3.1.<\/jats:p>","DOI":"10.1186\/s13041-020-00700-7","type":"journal-article","created":{"date-parts":[[2020,11,26]],"date-time":"2020-11-26T12:03:40Z","timestamp":1606392220000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Zonisamide can ameliorate the voltage-dependence alteration of the T-type calcium channel CaV3.1 caused by a mutation responsible for spinocerebellar ataxia"],"prefix":"10.1186","volume":"13","author":[{"given":"Naoyuki","family":"Hara","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5190-3547","authenticated-orcid":false,"given":"Hiroyuki","family":"Morino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukiko","family":"Matsuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichi","family":"Satoh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kouichi","family":"Hashimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirofumi","family":"Maruyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideshi","family":"Kawakami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,11,26]]},"reference":[{"key":"700_CR1","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1186\/s13041-015-0180-4","volume":"8","author":"H Morino","year":"2015","unstructured":"Morino H, Matsuda Y, Muguruma K, Miyamoto R, Ohsawa R, Ohtake T, et al. 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