{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:21Z","timestamp":1790208021835,"version":"4.1.0"},"reference-count":64,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,1,22]],"date-time":"2018-01-22T00:00:00Z","timestamp":1516579200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01NS085054"],"award-info":[{"award-number":["R01NS085054"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2018,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Purkinje neuron dysfunction is associated with cerebellar ataxia. In a mouse model of spinocerebellar ataxia type 1 (\n                      <jats:styled-content style=\"fixed-case\">SCA<\/jats:styled-content>\n                      1), reduced potassium channel function contributes to altered membrane excitability resulting in impaired Purkinje neuron spiking. We sought to determine the relationship between altered membrane excitability and motor dysfunction in\n                      <jats:styled-content style=\"fixed-case\">SCA<\/jats:styled-content>\n                      1 mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Patch\u2010clamp recordings in acute cerebellar slices and motor phenotype testing were used to identify pharmacologic agents which improve Purkinje neuron physiology and motor performance in\n                      <jats:styled-content style=\"fixed-case\">SCA<\/jats:styled-content>\n                      1 mice. Additionally, we retrospectively reviewed records of patients with\n                      <jats:styled-content style=\"fixed-case\">SCA<\/jats:styled-content>\n                      1 and other autosomal\u2010dominant\n                      <jats:styled-content style=\"fixed-case\">SCA<\/jats:styled-content>\n                      s with prominent Purkinje neuron involvement to determine whether currently approved potassium channel activators were tolerated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Activating calcium\u2010activated and subthreshold\u2010activated potassium channels improved Purkinje neuron spiking impairment in\n                      <jats:styled-content style=\"fixed-case\">SCA<\/jats:styled-content>\n                      1 mice (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.05). Additionally, dendritic hyperexcitability was improved by activating subthreshold\u2010activated potassium channels but not calcium\u2010activated potassium channels (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.01). Improving spiking and dendritic hyperexcitability through a combination of chlorzoxazone and baclofen produced sustained improvements in motor dysfunction in\n                      <jats:styled-content style=\"fixed-case\">SCA<\/jats:styled-content>\n                      1 mice (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.01). Retrospective review of\n                      <jats:styled-content style=\"fixed-case\">SCA<\/jats:styled-content>\n                      patient records suggests that co\u2010treatment with chlorzoxazone and baclofen is tolerated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>\n                      Targeting both altered spiking and dendritic membrane excitability is associated with sustained improvements in motor performance in\n                      <jats:styled-content style=\"fixed-case\">SCA<\/jats:styled-content>\n                      1 mice, while targeting altered spiking alone produces only short\u2010term improvements in motor dysfunction. Potassium channel activators currently in clinical use are well tolerated and may provide benefit in\n                      <jats:styled-content style=\"fixed-case\">SCA<\/jats:styled-content>\n                      patients. Future clinical trials with potassium channel activators are warranted in cerebellar ataxia.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acn3.527","type":"journal-article","created":{"date-parts":[[2018,1,22]],"date-time":"2018-01-22T11:51:26Z","timestamp":1516621886000},"page":"297-314","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Targeting potassium channels to treat cerebellar ataxia"],"prefix":"10.1002","volume":"5","author":[{"given":"David D.","family":"Bushart","sequence":"first","affiliation":[{"name":"Department of Molecular &amp; Integrative Physiology University of Michigan Ann Arbor Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravi","family":"Chopra","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Michigan Ann Arbor Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vikrant","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of California Davis California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey G.","family":"Murphy","sequence":"additional","affiliation":[{"name":"Department of Molecular &amp; Integrative Physiology University of Michigan Ann Arbor Michigan"},{"name":"Molecular &amp; Behavioral Neuroscience Institute University of Michigan Ann Arbor Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4437-5763","authenticated-orcid":false,"given":"Heike","family":"Wulff","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of California Davis California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vikram G.","family":"Shakkottai","sequence":"additional","affiliation":[{"name":"Department of Molecular &amp; Integrative Physiology University of Michigan Ann Arbor Michigan"},{"name":"Department of Neurology University of Michigan Ann Arbor Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,1,22]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddx281"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1357-15.2015"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2789-11.2011"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds427"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2990.1994.tb00955.x"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(10)70183-6"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2148"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19-05-01663.1999"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1999.tb11279.x"},{"issue":"20","key":"e_1_2_8_11_1","first-page":"S33","article-title":"Increased dendritic excitability and calcium\u2010dependent PKC activation: a novel mechanism underlying Purkinje neuron dendritic degeneration in cerebellar ataxias","volume":"80","author":"Chopra R","year":"2016","journal-title":"Ann Neurol"},{"key":"e_1_2_8_12_1","doi-asserted-by":"crossref","first-page":"P2.118","DOI":"10.1212\/WNL.84.14_supplement.P2.118","article-title":"A novel KNCMA1 mutation associated with progressive cerebellar ataxia","volume":"84","author":"Staisch J","year":"2015","journal-title":"Neurology"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1758"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.23700"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.23701"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.0030108"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26096"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2015.09.007"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13041-015-0180-4"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep29489"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2012.07.013"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181d31e23"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(15)00201-X"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.47.6_Suppl_4.233S"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(02)01987-8"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90273-2"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-12-04899.2003"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.2002.02171.x"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00127.2012"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.4161\/chan.3.6.9838"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1996.sp021713"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200420216"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2008.09.019"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.07596"},{"key":"e_1_2_8_35_1","first-page":"e52068","article-title":"Slice it hot: acute adult brain slicing in physiological temperature","volume":"30","author":"Ankri L","year":"2014","journal-title":"J Vis Exp"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00982.2009"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.6341-09.2010"},{"key":"e_1_2_8_38_1","volume-title":"Clinical Drug Information","author":"Lexicomp","year":"2017"},{"key":"e_1_2_8_39_1","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1111\/j.1532-5415.2012.03923.x","article-title":"American Geriatrics Society Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults","volume":"60","author":"Society TAG","year":"2012","journal-title":"J Am Geriatr Soc"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0401702101"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2003.00053.x"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(02)03730-7"},{"key":"e_1_2_8_43_1","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/S0022-3565(24)38803-2","article-title":"Modulation of recombinant small\u2010conductance Ca(2 + )\u2010activated K(+) channels by the muscle relaxant chlorzoxazone and structurally related compounds","volume":"296","author":"Cao Y","year":"2001","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2454-12.2012"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2004.081000"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.108.051425"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M010001200"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1001745107"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.108.143933"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0905-11.2011"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1999.tb11293.x"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1993.265.5.C1363"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00016.2014"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00021.2009"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2001.00381.x"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP272950"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn764"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182a55f6d"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000219042.60538.92"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1008605107"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.2001.85.4.1750"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3953-15.2016"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.26377"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31822e7ca0"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-8-177"}],"container-title":["Annals of Clinical and Translational Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Facn3.527","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acn3.527","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,29]],"date-time":"2025-06-29T19:34:05Z","timestamp":1751225645000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/acn3.527"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,1,22]]},"references-count":64,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2018,3]]}},"alternative-id":["10.1002\/acn3.527"],"URL":"https:\/\/doi.org\/10.1002\/acn3.527","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.732883577.793552248","asserted-by":"object"}]},"ISSN":["2328-9503","2328-9503"],"issn-type":[{"value":"2328-9503","type":"print"},{"value":"2328-9503","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,1,22]]},"assertion":[{"value":"2017-11-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-12-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-01-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}