Melatonin receptors activate heteromeric G-protein coupled Kir3 channels

Nelson, Cole S.; Marino, Jennifer L.; Allen, Charles N.

doi:10.1097/00001756-199602290-00009

Cited by 77 publications

(41 citation statements)

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“…Similar findings have been observed in rat cerebellar granule cells [99]. Melatonin activates potassium conductance and inhibits an inward cation current and rat SCN neuronal firing [100], and stimulation of the melatonin receptor has been shown to activate G protein-gated inwardly rectifying potassium channels (Kir3.1/Kir3.2 and Kir3.2/ Kir3.3) in a PTX-sensitive manner in Xenopus oocytes expressing cloned mammalian melatonin receptors MT 1 or Mel 1c [101]. Members of the Kir3 channel subfamily, which are widely expressed in the brain, can be activated by Gß 1Á2 via direct interaction, but not by other combinations of GßÁ subunits [102].…”

Section: Potassium Channelssupporting

confidence: 75%

G Protein-Linked Effector and Second Messenger Systems Involved in Melatonin Signal Transduction

New

Tsim

Wong³

2003

Neurosignals

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The isolation and characterization of multiple melatonin receptors in a wide range of tissues and cells signifies the functional diversity of melatonin. In different cellular environments, melatonin can regulate distinct second messengers or even positively or negatively regulate the same signal transduction pathway. The capacity by which melatonin receptors modulate the activities of various effector molecules is determined by the complement of signaling components present in any particular cell type. The specific interactions between many signaling molecules have been discerned in an increasing number of cellular systems and this information is being used to explain the physiological actions of melatonin. This review will attempt to summarize recent research by many groups that has revealed numerous subtleties of the melatonin-coupled signaling pathways.

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Section: Potassium Channelssupporting

confidence: 75%

G Protein-Linked Effector and Second Messenger Systems Involved in Melatonin Signal Transduction

New

Tsim

Wong³

2003

Neurosignals

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“…Inward-rectifier potassium channels (Kir) are also activated by melatonin. MT 1 melatonin receptors expressed in X. laevis oocytes (Nelson et al, 1996) or AtT20 cells ) activate Kir3 inward-rectifier potassium channels through a PTX-sensitive mechanism that may involve ␤␥ subunits of G i proteins. Activation of Kir3 channels may underlie melatonin-mediated increases in potassium conductance (Jiang et al, 1995) and may be the mechanism by which melatonin inhibits neuronal firing in the SCN (Mason and Brooks, 1988;Shibata et al, 1989;Stehle et al, 1989).…”

Section: A Mt 1 Melatonin Receptor Signalingmentioning

confidence: 99%

International Union of Basic and Clinical Pharmacology. LXXV. Nomenclature, Classification, and Pharmacology of G Protein-Coupled Melatonin Receptors

et al. 2010

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“…The inhibitory effect on the neuronal activity of SCN neurons is assumed to be caused by a hyperpolarization of the neurons mediated by activation of potassium conductance (Jiang et al, 1995;Nelson et al, 1996) and enhancement of GABA A receptor-induced membrane currents (Wan et al, 1999). The mechanisms, however, leading to the increase in neuronal activity in hippocampal neurons are completely unknown.…”

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confidence: 99%

Melatonin receptors in rat hippocampus: molecular and functional investigations

et al. 2002

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Since binding sites for melatonin have been found in the hippocampus of several mammals, it has been suggested that the pineal hormone melatonin is able to modulate neuronal functions of hippocampal cells. In order to get more insight into the role of melatonin for the functions of hippocampal cells, the following experiments were performed: male rats, maintained under a 12/12-h light-dark cycle, were sacrificed by decapitation at zeitgeber times (h) ZT2, ZT8, and ZT15 (ZT0 = lights on); for experiment 1, gene expression for melatonin receptors was detected in the hippocampus and in hippocampal subfields by means of the RT-PCR technique; for experiment 2, electrophysiological and pharmacological properties of melatonin receptors heterologously expressed in Xenopus oocytes after injection of mRNA from the hippocampus were analyzed by means of voltage clamp technique; and for experiment 3, effects of melatonin on the spontaneous firing rate of action potentials in the CA1 regions of hippocampal slices were analyzed by means of extracellular recordings. The RT-PCR data revealed that transcripts for both the MT1 and MT2 melatonin receptors are present in the dentate gyrus, CA3, and CA1 regions, and the subiculum of the hippocampus. Injection of mRNA from rat hippocampus into the Xenopus oocytes led to the functional reconstitution of melatonin-sensitive receptors, which activates calcium-dependent chloride inward currents. The melatonin responses were abolished by simultaneous administration of the antagonists 2-phenylmelatonin and luzindole, and were unaffected by the MT2 antagonist 4-phenyl-2-propionamidotetralin. Bath-applied melatonin (1 micromol/l) enhances the firing rate of neurons in the CA1 region. The effect was small in experiments performed at ZT8 (<2 times the initial level) and large in experiments performed at ZT15 (>6 times). The changes of neuronal firing rate induced by melatonin were completely suppressed with simultaneous administration of the melatonin receptor antagonist luzindole (10 micromol/l). The results indicate that melatonin may play an important role in modulating neuronal excitability in the hippocampus.

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Melatonin receptors activate heteromeric G-protein coupled Kir3 channels

Cited by 77 publications

References 0 publications

G Protein-Linked Effector and Second Messenger Systems Involved in Melatonin Signal Transduction

G Protein-Linked Effector and Second Messenger Systems Involved in Melatonin Signal Transduction

International Union of Basic and Clinical Pharmacology. LXXV. Nomenclature, Classification, and Pharmacology of G Protein-Coupled Melatonin Receptors

Melatonin receptors in rat hippocampus: molecular and functional investigations

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