Leak potassium channels regulate sleep duration

Abstract

A primary goal of sleep research is to understand the molecular basis of sleep. Although some sleep/wake-promoting circuits and secreted substances have been identified, the detailed molecular mechanisms underlying the regulation of sleep duration have been elusive. Here, to address these mechanisms, we developed a simple computational model of a cortical neuron with five channels and a pump, which recapitulates the cortical electrophysiological characteristics of slow-wave sleep (SWS) and wakefulness. Comprehensive bifurcation and detailed mathematical analyses predicted that leak K⁺ channels play a role in generating the electrophysiological characteristics of SWS, leading to a hypothesis that leak K⁺ channels play a role in the regulation of sleep duration. To test this hypothesis experimentally, we comprehensively generated and analyzed 14 KO mice, and found that impairment of the leak K⁺ channel (<i>Kcnk9</i>) decreased sleep duration. Based on these results, we hypothesize that leak K⁺ channels regulate sleep duration in mammals.