CIRCADIAN REGULATION OF CGMP-GATED ION CHANNELS

University Of Houston, Houston TX

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Abstract

DESCRIPTION (from the Applicant's Abstract): Circadian oscillators cause a posttranslational modulation in gating properties of cGMP-gated channels in chick retina cones, in which the affinity for cGMP is higher during the subjective night. Both Erk and CaMKII are part of the output pathway coupling the core circadian oscillator in the photoreceptors to the gating behavior of these channels. Circadian rhythms in retina are also mediated in part by dopamine (DA) and melatonin. Melatonin is synthesized and secreted by photoreceptors, while DA is synthesized and secreted by subpopulations of amacrine and/or interplexiform cells. Melatonin and DA levels are in antiphase during the circadian cycle. Melatonin does not produce any effect on photoreceptors, but DA evokes several direct effects on photoreceptors including the induction of light-like phase-shifts via D2 receptors. This research will further study the cellular mechanism underlying circadian regulation of cGMP-gated channels and the phase-dependent modulation of cGMP-gated channels by DA in the following specific aim: (1) to understand how the signal transduction pathways of Erk and CaMKII lead to clock control of channel gating properties of cGMP-gated channels, and (2) to identify mechanism of phase-dependent modulation of cGMP-gated channels by DA.