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Noradrenaline upregulates T‐type calcium channels in rat pinealocytes
Author(s) -
Yu Haijie,
Seo Jong Bae,
Jung SeungRyoung,
Koh DukSu,
Hille Bertil
Publication year - 2015
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2014.284208
Subject(s) - pinealocyte , l type calcium channel , calcium , t type calcium channel , endocrinology , chemistry , medicine , voltage dependent calcium channel , neuroscience , microbiology and biotechnology , biology , pineal gland , melatonin
Key points The mammalian pineal gland is a neuroendocrine organ that responds to circadian and seasonal rhythms. Its major function is to secrete melatonin as a hormonal night signal in response to nocturnal delivery of noradrenaline from sympathetic neurons. Culturing rat pinealocytes in noradrenaline for 24 h induced a low‐voltage activated transient Ca 2+ current whose pharmacology and kinetics corresponded to a Ca V 3.1 T‐type channel. The upregulation of the T‐type Ca 2+ current is initiated by β‐adrenergic receptors, cyclic AMP and cyclic AMP‐dependent protein kinase. Messenger RNA for Ca V 3.1 T‐type channels is significantly elevated by noradrenaline at 8 h and 24 h. The noradrenaline‐induced T‐type channel mediated an increased Ca 2+ entry and supported modest transient electrical responses to depolarizing stimuli, revealing the potential for circadian regulation of pinealocyte electrical excitability and Ca 2+ signalling.Abstract Our basic hypothesis is that mammalian pinealocytes have cycling electrical excitability and Ca 2+ signalling that may contribute to the circadian rhythm of pineal melatonin secretion. This study asked whether the functional expression of voltage‐gated Ca 2+ channels (Ca V channels) in rat pinealocytes is changed by culturing them in noradrenaline (NA) as a surrogate for the night signal. Channel activity was assayed as ionic currents under patch clamp and as optical signals from a Ca 2+ ‐sensitive dye. Channel mRNAs were assayed by quantitative polymerase chain reaction. Cultured without NA, pinealocytes showed only non‐inactivating L‐type dihydropyridine‐sensitive Ca 2+ current. After 24 h in NA, additional low‐voltage activated transient Ca 2+ current developed whose pharmacology and kinetics corresponded to a T‐type Ca V 3.1 channel. This change was initiated by β‐adrenergic receptors, cyclic AMP and protein kinase A as revealed by pharmacological experiments. mRNA for Ca V 3.1 T‐type channels became significantly elevated, but mRNA for another T‐type channel and for the major L‐type channel did not change. After only 8 h of NA treatment, the Ca V 3.1 mRNA was already elevated, but the transient Ca 2+ current was not. Even a 16 h wait without NA following the 8 h NA treatment induced little additional transient current. However, these cells were somehow primed to make transient current as a second NA exposure for only 60 min sufficed to induce large T‐type currents. The NA‐induced T‐type channel mediated an increased Ca 2+ entry during short depolarizations and supported modest transient electrical responses to depolarizing stimuli. Such experiments reveal the potential for circadian regulation of excitability.