| Autor: |
Yu, Haijie, Seo, Jong Bae, Jung, Seung‐Ryoung, Koh, Duk‐Su, Hille, Bertil |
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| Zdroj: |
Journal of Physiology; Feb2015, Vol. 593 Issue 4, p887-904, 18p |
| Abstrakt: |
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 Ca2+ current whose pharmacology and kinetics corresponded to a CaV3.1 T-type channel., The upregulation of the T-type Ca2+ current is initiated by β-adrenergic receptors, cyclic AMP and cyclic AMP-dependent protein kinase., Messenger RNA for CaV3.1 T-type channels is significantly elevated by noradrenaline at 8 h and 24 h., The noradrenaline-induced T-type channel mediated an increased Ca2+ entry and supported modest transient electrical responses to depolarizing stimuli, revealing the potential for circadian regulation of pinealocyte electrical excitability and Ca2+ signalling., Abstract Our basic hypothesis is that mammalian pinealocytes have cycling electrical excitability and Ca2+ signalling that may contribute to the circadian rhythm of pineal melatonin secretion. This study asked whether the functional expression of voltage-gated Ca2+ channels (CaV 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 Ca2+-sensitive dye. Channel mRNAs were assayed by quantitative polymerase chain reaction. Cultured without NA, pinealocytes showed only non-inactivating L-type dihydropyridine-sensitive Ca2+ current. After 24 h in NA, additional low-voltage activated transient Ca2+ current developed whose pharmacology and kinetics corresponded to a T-type CaV3.1 channel. This change was initiated by β-adrenergic receptors, cyclic AMP and protein kinase A as revealed by pharmacological experiments. mRNA for CaV3.1 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 CaV3.1 mRNA was already elevated, but the transient Ca2+ 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 Ca2+ entry during short depolarizations and supported modest transient electrical responses to depolarizing stimuli. Such experiments reveal the potential for circadian regulation of excitability. [ABSTRACT FROM AUTHOR] |
| Databáze: |
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