Abstract
Abstract: :
Purpose: Light hyperpolarizes photoreceptor membrane, and this is an essential cellular signal for vision in vertebrates. It is not clear, however, whether changes in membrane potential play roles in entrainment of photoreceptor circadian oscillator. We investigated effects of membrane depolarization caused by high extracellular potassium treatment on circadian rhythms of melatonin. Methods: The Xenopus retinal photoreceptor layers were cultured in a flow-through culture system under constant darkness for 5 days. On the second day in culture, a 4-h pulse of high [K+] was applied to the photoreceptor layers at the time specified, and both phases and levels of melatonin rhythms after the pulse were compared with those of untreated control group. Results: A 4-h pulse of high [K+] (+15 mM or +34 mM) beginning at the late subjective day (ZT 9) caused dose-dependent phase advances of melatonin rhythms. This effect is phase-dependent, and the identical pulse (+34 mM) beginning at the subjective night did not reset the melatonin rhythms, showing a phase-dependent manner similar to dark. However, no phase-delay was observed by the high [K+] treatment under our experimental condition. The high [K+] treatment also increased melatonin release from photoreceptors. In contrast to the phase-shifting effect, the stimulatory effect on the melatonin levels did not depend on the timing of the pulse, and the high [K+] treatment given at any time of the day increased melatonin levels. Conclusions: These results suggest that membrane depolarization of retinal photoreceptor plays roles for entrainment of the circadian oscillator and for regulation of melatonin release, and that depolarization signal mediates dark information to the photoreceptor circadian system.
Keywords: circadian rhythms • photoreceptors • melatonin