{"id":2198,"date":"2018-03-19T00:00:03","date_gmt":"2018-03-19T00:00:03","guid":{"rendered":"http:\/\/bergleslab.com\/?p=2198"},"modified":"2018-06-04T19:35:02","modified_gmt":"2018-06-04T19:35:02","slug":"larson-2018","status":"publish","type":"post","link":"http:\/\/bergleslab.com\/index.php\/2018\/03\/19\/larson-2018\/","title":{"rendered":"Oligodendrocytes control potassium accumulation in white matter and seizure susceptibility"},"content":{"rendered":"
Elife.<\/a>\u00a02018 Mar 29;7. pii: e34829. doi: 10.7554\/eLife.34829.<\/div>\n

Oligodendrocytes control potassium accumulation in white matter and seizure susceptibility.<\/h4>\n
Larson VA<\/a>1<\/sup>,\u00a0Mironova Y<\/a>1<\/sup>,\u00a0Vanderpool KG<\/a>2<\/sup>,\u00a0Waisman A<\/a>3<\/sup>,\u00a0Rash JE<\/a>2<\/sup>,\u00a0Agarwal A<\/a>1<\/sup>,\u00a0Bergles DE<\/a>1<\/sup>.<\/div>\n
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<\/h4>\n

Abstract<\/h4>\n

The inwardly rectifying K+<\/sup>\u00a0channel Kir<\/sub>4.1 is broadly expressed by CNS glia and deficits in Kir<\/sub>4.1 lead to seizures and myelin vacuolization. However, the role of oligodendrocyte Kir<\/sub>4.1 channels in controlling myelination and K+<\/sup>\u00a0clearance in white matter has not been defined. Here, we show that selective deletion of Kir<\/sub>4.1 from oligodendrocyte progenitors (OPCs) or mature oligodendrocytes did not impair their development or disrupt the structure of myelin. However, mice lacking oligodendrocyte Kir<\/sub>4.1 channels exhibited profound functional impairments, including slower clearance of extracellular K+<\/sup>\u00a0and delayed recovery of axons from repetitive stimulation in white matter, as well as spontaneous seizures, a lower seizure threshold, and activity-dependent motor deficits. These results indicate that Kir<\/sub>4.1 channels in oligodendrocytes play an important role in extracellular K+<\/sup>\u00a0homeostasis in white matter, and that selective loss of this channel from oligodendrocytes is sufficient to impair K+<\/sup>\u00a0clearance and promote seizures.<\/p>\n<\/div>\n

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 <\/p>\n

1 The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United States.<\/p>\n

2 Department of Biomedical Sciences, Colorado State University, Fort Collins, United States.<\/p>\n

3 Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.<\/p>\n

PDF<\/a><\/p>\n<\/div>\n","protected":false},"excerpt":{"rendered":"

The inwardly rectifying K+ channel Kir4.1 is broadly expressed by CNS glia and deficits in Kir4.1 lead to seizures and myelin vacuolization. However, the role of oligodendrocyte Kir4.1 channels in controlling myelination and K+ clearance in white matter has not been defined. Here, we show that selective deletion of Kir4.1 from oligodendrocyte progenitors (OPCs) or mature oligodendrocytes did not impair their development or disrupt the structure of myelin. However, mice lacking oligodendrocyte Kir4.1 channels exhibited profound functional impairments, including slower clearance of extracellular K+ and delayed recovery of axons from repetitive stimulation in white matter, as well as spontaneous seizures, a lower seizure threshold, and activity-dependent motor deficits. These results indicate that Kir4.1 channels in oligodendrocytes play an important role in extracellular K+ homeostasis in white matter, and that selective loss of this channel from oligodendrocytes is sufficient to impair K+ clearance and promote seizures.<\/p>\n","protected":false},"author":1,"featured_media":2203,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[78,33],"tags":[135,136,60,124,49,134],"class_list":["post-2198","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-original-research","category-publications","tag-epilepsy","tag-kir4-1","tag-myelination","tag-oligodendrocytes","tag-potassium","tag-seizure"],"_links":{"self":[{"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/posts\/2198","targetHints":{"allow":["GET"]}}],"collection":[{"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/comments?post=2198"}],"version-history":[{"count":4,"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/posts\/2198\/revisions"}],"predecessor-version":[{"id":2204,"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/posts\/2198\/revisions\/2204"}],"wp:featuredmedia":[{"embeddable":true,"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/media\/2203"}],"wp:attachment":[{"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/media?parent=2198"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/categories?post=2198"},{"taxonomy":"post_tag","embeddable":true,"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/tags?post=2198"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}