Abstract
Abstract : Photoreceptors of the chick pineal are one of the only vertebrate intrinsic circadian oscillators amenable to cellular analysis. We characterized the electrophysiological properties of these cells using patch clamp and fura-2 recording techniques. We analyzed several types of voltage-and cGMP-activated ionic channels, and obtained evidence that cGMP-activated channels participate in phototransduction. We also examined intracellular Ca2+ dynamics and obtained evidence for the existence of intracellular Ca2+ stores and Ca2+ oscillations that can be mobilized by drugs and hormones that increase cAMP and promote melatonin secretion. Norepinephrine, which inhibits melatonin secretion, had no effect on Ca2+ dynamics. Most importantly, we discovered a new type of ionic channel, ILOT, whose gating is under direct circadian control. ILOT is permeable to Ca2+, but its gating is not controlled by membrane potential or intracellular ligands. ILOT has unusual kinetic properties, as it can stay open for seconds at a time. This feature is not seen in other types of ionic channels. ILOT is only active in the nighttime, even in pineal cells free-running in constant-dark conditions. ILOT is also present in chick retinal photoreceptors, which also contain a circadian oscillator. ILOT therefore represents a logical target for pharmacological manipulation of circadian output.
Published Version
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