Modulation of Ca2+ oscillation and melatonin secretion by BKCa channel activity in rat pinealocytes

The pineal glands regulate circadian rhythm through the synthesis and secretion of melatonin. The stimulation of nicotinic acetylcholine receptor due to parasympathetic nerve activity causes an increase in intracellular Ca2+ concentration and eventually downregulates melatonin production. Our previous report shows that rat pinealocytes have spontaneous and nicotine-induced Ca2+ oscillations that are evoked by membrane depolarization followed by Ca2+ influx through voltage-dependent Ca2+ channels (VDCCs). These Ca2+ oscillations are supposed to contribute to the inhibitory mechanism of melatonin secretion. Here we examined the involvement of large-conductance Ca2+-activated K+ (BKCa) channel conductance on the regulation of Ca2+ oscillation and melatonin production in rat pinealocytes. Spontaneous Ca2+ oscillations were markedly enhanced by BKCa channel blockers (1 μM paxilline or 100 nM iberiotoxin). Nicotine (100 μM)-induced Ca2+ oscillations were also augmented by paxilline. In contrast, spontaneous Ca2+ oscillations were abolished by BKCa channel opener [3 μM 12,14-dichlorodehydroabietic acid (diCl-DHAA)]. Under whole cell voltage-clamp configurations, depolarization-elicited outward currents were significantly activated by diCl-DHAA and blocked by paxilline. Expression analyses revealed that the α and β3 subunits of BKCa channel were highly expressed in rat pinealocytes. Importantly, the activity of BKCa channels modulated melatonin secretion from whol...
Source: AJP: Cell Physiology - Category: Cytology Authors: Tags: ARTICLES Source Type: research