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- Title
Characterization of hyperpolarization-activated cyclic nucleotide-gated channels in oligodendrocytes.
- Authors
Lyman, Kyle A.; Ye Han; Robinson, Andrew P.; Weinberg, Samuel E.; Fisher, Daniel W.; Heuermann, Robert J.; Lyman, Reagan E.; Dong Kyu Kim; Ludwig, Andreas; Chandel, Navdeep S.; Does, Mark D.; Miller, Stephen D.; Chetkovich, Dane M.
- Abstract
Mature oligodendrocytes (OLG) are the myelin-forming cells of the central nervous system. Recent work has shown a dynamic role for these cells in the plasticity of neural circuits, leading to a renewed interest in voltage-sensitive currents in OLG. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels and their respective current (Ih) were recently identified in mature OLG and shown to play a role in regulating myelin length. Here we provide a biochemical and electrophysiological characterization of HCN channels in cells of the oligodendrocyte lineage. We observed that mice with a nonsense mutation in the Hcn2 gene (Hcn2ap/ap) have less white matter than their wild type counterparts with fewer OLG and fewer oligodendrocyte progenitor cells (OPCs). Hcn2ap/ap mice have severe motor impairments, although these deficits were not observed in mice with HCN2 conditionally eliminated only in oligodendrocytes (Cnpcre/+; Hcn2F/F). However, Cnpcre/+; Hcn2F/F mice develop motor impairments more rapidly in response to experimental autoimmune encephalomyelitis (EAE). We conclude that HCN2 channels in OLG may play a role in regulating metabolism.
- Subjects
CENTRAL nervous system; NEURAL circuitry; NONSENSE mutation; OLIGODENDROGLIA; WHITE matter (Nerve tissue); MYELIN oligodendrocyte glycoprotein; PROGENITOR cells; MYELIN proteins
- Publication
Frontiers in Cellular Neuroscience, 2024, p1
- ISSN
1662-5102
- Publication type
Article
- DOI
10.3389/fncel.2024.1321682