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

Autor: Hiroya Mizutani, Hisao Yamamura, Makoto Muramatsu, Yuji Imaizumi, Yumiko Hagihara, Yoshiaki Suzuki
Rok vydání: 2016
Předmět:
Zdroj: American Journal of Physiology-Cell Physiology. 310:C740-C747
ISSN: 1522-1563
0363-6143
Popis: 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 BKCachannel 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 BKCachannel 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 BKCachannel were highly expressed in rat pinealocytes. Importantly, the activity of BKCachannels modulated melatonin secretion from whole pineal gland of the rat. Taken together, BKCachannel activation attenuates these Ca2+oscillations due to depolarization-synchronized Ca2+influx through VDCCs and results in a recovery of reduced melatonin secretion during parasympathetic nerve activity. BKCachannels may play a physiological role for melatonin production via a negative-feedback mechanism.
Databáze: OpenAIRE