Involvement of small-conductance Ca 2+ -activated K + (SK Ca 2) channels in spontaneous Ca 2+ oscillations in rat pinealocytes.

Melatonin secretion from the pineal glands regulates circadian rhythms in mammals. Melatonin production is decreased by an increase in cytosolic Ca ²⁺ concentration following the activation of nicotinic acetylcholine receptors in parasympathetic systems. We previously reported that pineal Ca ²⁺ oscillations were regulated by voltage-dependent Ca ²⁺ channels and large-conductance Ca ²⁺ -activated K ⁺ (BK _Ca ) channels, which inhibited melatonin production. In the present study, the contribution of small- and intermediate-conductance Ca ²⁺ -activated K ⁺ (SK _Ca and IK _Ca ) channels to the regulation of spontaneous Ca ²⁺ oscillations was examined in rat pinealocytes. The amplitude and frequency of spontaneous Ca ²⁺ oscillations were increased by a SK _Ca channel blocker (100 nM apamin), but not by an IK _Ca channel blocker (1 μM TRAM-34). On the other hand, they were decreased by a SK _Ca channel opener (100 μM DCEBIO), but not by an IK _Ca channel opener (1 μM DCEBIO). Expression analyses using quantitative real-time PCR, immunocytochemical staining, and Western blotting revealed that the SK _Ca 2 channel subtype was abundantly expressed in rat pinealocytes. Moreover, the enhanced amplitude of Ca ²⁺ oscillations in the presence of apamin was further increased by a BK _Ca channel blocker (1 μM paxilline). These results suggest that the activity of SK _Ca 2 channels regulates cytosolic Ca ²⁺ signaling and melatonin production during parasympathetic activation in pineal glands.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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