抄録
Orexin-A and orexin-B, also called hypocretin-1 and hypocretin-2, act upon orexin receptor-1 and orexin receptor-2 in the brain, and participate in the regulation of feeding and sleep-wakefulness. Although orexin-containing neurons identified in the lateral hypothalamus project to the pedunculopontine tegmental nucleus (PPT), which is one of brain sites that control sleep-wakefulness, the action of orexins on PPT neurons is not known. Thus, we examined effects of orexins on PPT neurons using rat brain slice preparations and whole-cell patch clamp recording technique. Applications of orexin-A and orexin-B depolarized PPT neurons dose-dependently, and EC50 values were greater for orexin-B than for orexin-A. The depolarization was associated with the increase in membrane resistance. When extracellular K+ concentration was increased and/or extracellular Na+ was replaced by N-methyl-D-glucamine (NMDG), the magnitude of the depolarization significantly decreased or disappeared. In addition, when extracellular K+ concentration was increased and intracellular Ca2+ was chelated by BAPTA contained in pipette solution, the magnitude of the depolarization decreased, but not disappeared. These results suggest that orexins affect to K+ channel and non-selective cation channel on PPT neurons via orexin receptor-1, and participate in the regulation of sleep-wakefulness via the excitatory effect on PPT neurons. [J Physiol Sci. 2007;57 Suppl:S80]
