AUTHOR=Lyman Kyle A. , Han Ye , Robinson Andrew P. , Weinberg Samuel E. , Fisher Daniel W. , Heuermann Robert J. , Lyman Reagan E. , Kim Dong Kyu , Ludwig Andreas , Chandel Navdeep S. , Does Mark D. , Miller Stephen D. , Chetkovich Dane M. 

TITLE=Characterization of hyperpolarization-activated cyclic nucleotide-gated channels in oligodendrocytes

JOURNAL=Frontiers in Cellular Neuroscience

VOLUME=18

YEAR=2024

URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2024.1321682

DOI=10.3389/fncel.2024.1321682

ISSN=1662-5102

ABSTRACT=<p>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 (I<sub><italic>h</italic></sub>) 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 <italic>Hcn2</italic> gene (<italic>Hcn2<sup>ap/ap</sup></italic>) have less white matter than their wild type counterparts with fewer OLG and fewer oligodendrocyte progenitor cells (OPCs). <italic>Hcn2<sup>ap/ap</sup></italic> mice have severe motor impairments, although these deficits were not observed in mice with HCN2 conditionally eliminated only in oligodendrocytes (<italic>Cnp</italic><sup><italic>cre</italic>/+</sup>; <italic>Hcn2<sup>F/F</sup></italic>). However, <italic>Cnp</italic><sup><italic>cre</italic>/+</sup>; <italic>Hcn2<sup>F/F</sup></italic> 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.</p>