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IA Channels Encoded by Kv1.4 and Kv4.2 Regulate Circadian Period of PER2 Expression in the Suprachiasmatic Nucleus.
Granados-Fuentes, Daniel; Hermanstyne, Tracey O; Carrasquillo, Yarimar; Nerbonne, Jeanne M; Herzog, Erik D.
Afiliación
  • Granados-Fuentes D; Department of Biology, Washington University, St. Louis, MO, USA dgranado@wustl.edu.
  • Hermanstyne TO; Department of Biology, Washington University, St. Louis, MO, USA Departments of Medicine and Developmental Biology, Washington University, St. Louis, MO, USA.
  • Carrasquillo Y; Departments of Medicine and Developmental Biology, Washington University, St. Louis, MO, USA.
  • Nerbonne JM; Departments of Medicine and Developmental Biology, Washington University, St. Louis, MO, USA.
  • Herzog ED; Department of Biology, Washington University, St. Louis, MO, USA.
J Biol Rhythms ; 30(5): 396-407, 2015 Oct.
Article en En | MEDLINE | ID: mdl-26152125
Neurons in the suprachiasmatic nucleus (SCN), the master circadian pacemaker in mammals, display daily rhythms in electrical activity with more depolarized resting potentials and higher firing rates during the day than at night. Although these daily variations in the electrical properties of SCN neurons are required for circadian rhythms in physiology and behavior, the mechanisms linking changes in neuronal excitability to the molecular clock are not known. Recently, we reported that mice deficient for either Kcna4 (Kv1.4(-/-)) or Kcnd2 (Kv4.2(-/-); but not Kcnd3, Kv4.3(-/-)), voltage-gated K(+) (Kv) channel pore-forming subunits that encode subthreshold, rapidly activating, and inactivating K(+) currents (IA), have shortened (0.5 h) circadian periods in SCN firing and in locomotor activity compared with wild-type (WT) mice. In the experiments here, we used a mouse (Per2(Luc)) line engineered with a bioluminescent reporter construct, PERIOD2::LUCIFERASE (PER2::LUC), replacing the endogenous Per2 locus, to test the hypothesis that the loss of Kv1.4- or Kv4.2-encoded IA channels also modifies circadian rhythms in the expression of the clock protein PERIOD2 (PER2). We found that SCN explants from Kv1.4(-/-)Per2(Luc) and Kv4.2(-/-) Per2(Luc), but not Kv4.3(-/-)Per2(Luc), mice have significantly shorter (by approximately 0.5 h) circadian periods in PER2 rhythms, compared with explants from Per2(Luc) mice, revealing that the membrane properties of SCN neurons feedback to regulate clock (PER2) expression. The combined loss of both Kv1.4- and Kv4.2-encoded IA channels in Kv1.4(-/-)/Kv4.2(-/-)Per2(Luc) SCN explants did not result in any further alterations in PER2 rhythms. Interestingly, however, mice lacking both Kv1.4 and Kv4.2 show a striking (approximately 1.8 h) advance in their daily activity onset in a light cycle compared with WT mice, suggesting additional roles for Kv1.4- and Kv4.2-encoded IA channels in controlling the light-dependent responses of neurons within and/or outside of the SCN to regulate circadian phase of daily activity.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Núcleo Supraquiasmático / Ritmo Circadiano / Canal de Potasio Kv1.4 / Canales de Potasio Shal / Proteínas Circadianas Period Límite: Animals Idioma: En Revista: J Biol Rhythms Asunto de la revista: FISIOLOGIA Año: 2015 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Núcleo Supraquiasmático / Ritmo Circadiano / Canal de Potasio Kv1.4 / Canales de Potasio Shal / Proteínas Circadianas Period Límite: Animals Idioma: En Revista: J Biol Rhythms Asunto de la revista: FISIOLOGIA Año: 2015 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos