A cationic channel regulated by a vertebrate intrinsic circadian oscillator

SECRETORY cells of the chicken pineal gland exhibit light sensitive circadian rhythms in melatonin release that persist in vitro(1-12). Melatonin secretion is positively regulated by cyclic AMP and intracellular Ca2+ (refs 8, 10-15), Cyclic AMP analogues are more effective at stimulating melatonin secretion during the circadian night owing in part to increased Ca2+ influx at those times(12), However, this cannot be attributed to increased activity of L-type Ca2+ channels(12). Here we describe an unusual 40-pS cationic channel (I-LOT) in cultured chicken pineal cells that is permeable to Ca2+ and active in the night but not during the day, I-LOT is not voltage- or stretch-activated, it has a characteristically long open time, and its gating persists in excised inside-out patches in the absence of Ca2+ or cyclic nucleotides. Daily rhythms in I-LOT gating are also observed in previously entrained chicken pineal cells free-running under constant dark conditions. Nighttime I-LOT activity is not suppressed by brief Light pulses.