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

Abstract

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 Ca(2+) concentration and eventually downregulates melatonin production. Our previous report shows that rat pinealocytes have spontaneous and nicotine-induced Ca(2+) oscillations that are evoked by membrane depolarization followed by Ca(2+) influx through voltage-dependent Ca(2+) channels (VDCCs). These Ca(2+) oscillations are supposed to contribute to the inhibitory mechanism of melatonin secretion. Here we examined the involvement of large-conductance Ca(2+)-activated K(+) (BKCa) channel conductance on the regulation of Ca(2+) oscillation and melatonin production in rat pinealocytes. Spontaneous Ca(2+) oscillations were markedly enhanced by BKCa channel blockers (1 μM paxilline or 100 nM iberiotoxin). Nicotine (100 μM)-induced Ca(2+) oscillations were also augmented by paxilline. In contrast, spontaneous Ca(2+) 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 whole pineal gland of the rat. Taken together, BKCa channel activation attenuates these Ca(2+) oscillations due to depolarization-synchronized Ca(2+) influx through VDCCs and results in a recovery of reduced melatonin secretion during parasympathetic nerve activity. BKCa channels may play a physiological role for melatonin production via a negative-feedback mechanism.

Transcriptome-based screening of ion channels and transporters in a migratory chondroprogenitor cell line isolated from late-stage osteoarthritic cartilage

“…Since BK channels have been implicated in driving MSC differentiation (Pchelintseva & Djamgoz, 2018), perhaps the fact that CPCs are more committed to the chondrogenic lineage than undifferentiated MSCs may explain the higher levels of KCNMA1 both at the transcript and at the protein level (Matta et al, 2019). In addition, BK channel function was reported to modulate [Ca 2+ ] i oscillations in various cell types (Mizutani et al, 2016;Wakle-Prabagaran et al, 2016). Since we previously detected periodic uctuations in resting cytosolic Ca 2+ levels in CPCs (Matta et al, 2015), MaxiK channels may also play a central role in setting the RMP and modulating cell volume following the activation of purinergic signalling in CPCs.…”

The Hyperglycemic Effect of Melatonin in the Chinese Mitten Crab, Eriocheir sinensis

“…Melatonin (5-methoxy-N-acetyltryptamine, MT), is a highly conserved and ubiquitous molecule present from unicellular organisms to mammals. In vertebrate species, circulating plasma MT is synthesized principally in the pineal gland (Hardeland et al, 2011 ; Erren and Reiter, 2015 ; Mizutani et al, 2016 ), whereas it is mainly released from the optic ganglia of eyestalk in invertebrate species (Maciel F. E. et al, 2008 ). Moreover, it has been shown that it can also be released from peripheral tissues such as the cerebroid ganglion (Mendoza-Vargas et al, 2017 ), intestine (Lardone et al, 2014 ) and hemolymph (Mendoza-Vargas et al, 2017 ) in crustaceans (Balzer et al, 1997 ; Tilden et al, 1997 ).…”

Reciprocal Relationship between Ca²⁺ Signaling and Ca²⁺-Gated Ion Channels as a Potential Target for Drug Discovery

“…96) Spontaneous and/or nicotine-induced Ca 2+ oscillations, which are regulated by BK channel activity, have been detected in some primary cultured pineal cells of the rat. 97,98) TMEM16A and TMEM16B channels, presumably as a heterodimer, contribute to Ca 2+ signaling, which regulates melatonin secretion, 99) suggesting the potential contribution of these channels to circadian rhythms.…”