Kv12-encoded K+ channels drive the day-night switch in the repetitive firing rates of SCN neurons.

Autor:	Hermanstyne TO; Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, USA., Yang ND; Cardiovascular Division, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.; Department of Biomedical Engineering, Washington University, St. Louis, MO, USA., Granados-Fuentes D; Department of Biology, Washington University, St. Louis, MO, USA., Li X; Department of Biology, The Pennsylvania State University, University Park, State College, PA, USA., Mellor RL; Cardiovascular Division, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA., Jegla T; Department of Biology, The Pennsylvania State University, University Park, State College, PA, USA., Herzog ED; Department of Biology, Washington University, St. Louis, MO, USA., Nerbonne JM; Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, USA.; Cardiovascular Division, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.; Department of Biomedical Engineering, Washington University, St. Louis, MO, USA.
Jazyk:	angličtina
Zdroj:	The Journal of general physiology [J Gen Physiol] 2023 Sep 04; Vol. 155 (9). Date of Electronic Publication: 2023 Jul 26.
DOI:	10.1085/jgp.202213310
Abstrakt:	Considerable evidence suggests that day-night rhythms in the functional expression of subthreshold potassium (K+) channels regulate daily oscillations in the spontaneous firing rates of neurons in the suprachiasmatic nucleus (SCN), the master circadian pacemaker in mammals. The K+ conductance(s) driving these daily rhythms in the repetitive firing rates of SCN neurons, however, have not been identified. To test the hypothesis that subthreshold Kv12.1/Kv12.2-encoded K+ channels play a role, we obtained current-clamp recordings from SCN neurons in slices prepared from adult mice harboring targeted disruptions in the Kcnh8 (Kv12.1-/-) or Kcnh3 (Kv12.2-/-) locus. We found that mean nighttime repetitive firing rates were higher in Kv12.1-/- and Kv12.2-/- than in wild type (WT), SCN neurons. In marked contrast, mean daytime repetitive firing rates were similar in Kv12.1-/-, Kv12.2-/-, and WT SCN neurons, and the day-night difference in mean repetitive firing rates, a hallmark feature of WT SCN neurons, was eliminated in Kv12.1-/- and Kv12.2-/- SCN neurons. Similar results were obtained with in vivo shRNA-mediated acute knockdown of Kv12.1 or Kv12.2 in adult SCN neurons. Voltage-clamp experiments revealed that Kv12-encoded current densities in WT SCN neurons are higher at night than during the day. In addition, the pharmacological block of Kv12-encoded currents increased the mean repetitive firing rate of nighttime, but not daytime, in WT SCN neurons. Dynamic clamp-mediated subtraction of modeled Kv12-encoded currents also selectively increased the mean repetitive firing rates of nighttime WT SCN neurons. Despite the elimination of the nighttime decrease in the mean repetitive firing rates of SCN neurons, however, locomotor (wheel-running) activity remained rhythmic in Kv12.1-/-, Kv12.2-/-, and Kv12.1-targeted shRNA-expressing, and Kv12.2-targeted shRNA-expressing animals. (© 2023 Hermanstyne et al.)
Databáze:	MEDLINE
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