Increased functional coupling of 5-HT1A autoreceptors to GIRK channels in Tph2-/- mice
Mlinar B., Montalbano A., Waider J., Lesh K. Yu., Corradetti R.
European Neuropsychopharmacology
Vol.27, Issue12, P. 1258-1267
Опубликовано: 2017
Тип ресурса: Статья
DOI:10.1016/j.euroneuro.2017.10.033
Аннотация:
Firing activity of serotonergic neurons is under regulatory control by somatodendritic 5-HT1A autoreceptors (5-HT1AARs). Enhanced 5-HT1AAR functioning may cause decreased serotonergic signaling in brain and has thereby been implicated in the etiology of mood and anxiety disorders. Tryptophan hydroxylase-2 knockout (Tph2-/-) mice exhibit sensitization of 5-HT1A agonist-induced inhibition of serotonergic neuron firing and thus represents a unique animal model of enhanced 5-HT1AAR functioning. To elucidate the mechanisms underlying 5-HT1AAR supersensitivity in Tph2-/- mice, we characterized the activation of G protein-coupled inwardly-rectifying potassium (GIRK) conductance by the 5-HT1A receptor agonist 5-carboxamidotryptamine using whole-cell recordings from serotonergic neurons in dorsal raphe nucleus. Tph2-/- mice exhibited a mean twofold leftward shift of the agonist concentration–response curve (p < 0.001) whereas the maximal response, proportional to the 5-HT1AAR number, was not
Ключевые слова:
5-HT1A Receptor; Anxiety; Depression; Dorsal raphe; G-Protein; Kir3 Potassium Channel
5 carbamoyltryptamine; autoreceptor; G protein coupled inwardly rectifying potassium channel; guanosine 5' o (3 thiotriphosphate); serotonin 1A agonist; serotonin 1A receptor; tryptophan hydroxylase 2; 4 aminobutyric acid receptor blocking agent; 5-carboxamidotryptamine; benzyl[3 [[1 (3,4 dichlorophenyl)ethyl]amino] 2 hydroxypropyl]phosphinic acid; G protein coupled inwardly rectifying potassium channel; phosphinic acid derivative; propanolamine derivative; serotonin; serotonin 1A receptor; serotonin receptor affecting agent; Tph2 protein, mouse; tryptophan hydroxylase; alpha adrenergic stimulation; animal experiment; Article; concentration response; controlled study; depression; female; knockout mouse; male; mouse; mouse model; nonhuman; potassium conductance; priority journal; receptor density; sensitization; serotoninergic nerve cell; serotoninergic system; action potential; analogs and derivatives; animal; biophysics; cytology; deficiency; dorsal raphe nucleus; dose response; drug
Язык текста: Английский
ISSN: 1873-7862
Mlinar B.
Montalbano A.
Waider J.
Lesh K. Yu. Klaus-Peter Yulius 1957-
Corradetti R.
Млинар Б.
Монталбано А.
Wаидер Й.
Леш К. Ю. Клаус-Петер Юлиус 1957-
Cоррадетти Р.
Increased functional coupling of 5-HT1A autoreceptors to GIRK channels in Tph2-/- mice
Текст визуальный непосредственный
European Neuropsychopharmacology
Elsevier Science Publisher B.V.
Vol.27, Issue12 P. 1258-1267
2017
Статья
5-HT1A Receptor Anxiety Depression Dorsal raphe G-Protein Kir3 Potassium Channel
5 carbamoyltryptamine autoreceptor G protein coupled inwardly rectifying potassium channel guanosine 5' o (3 thiotriphosphate) serotonin 1A agonist serotonin 1A receptor tryptophan hydroxylase 2 4 aminobutyric acid receptor blocking agent 5-carboxamidotryptamine benzyl[3 [[1 (3,4 dichlorophenyl)ethyl]amino] 2 hydroxypropyl]phosphinic acid G protein coupled inwardly rectifying potassium channel phosphinic acid derivative propanolamine derivative serotonin serotonin 1A receptor serotonin receptor affecting agent Tph2 protein, mouse tryptophan hydroxylase alpha adrenergic stimulation animal experiment Article concentration response controlled study depression female knockout mouse male mouse mouse model nonhuman potassium conductance priority journal receptor density sensitization serotoninergic nerve cell serotoninergic system action potential analogs and derivatives animal biophysics cytology deficiency dorsal raphe nucleus dose response drug
Firing activity of serotonergic neurons is under regulatory control by somatodendritic 5-HT1A autoreceptors (5-HT1AARs). Enhanced 5-HT1AAR functioning may cause decreased serotonergic signaling in brain and has thereby been implicated in the etiology of mood and anxiety disorders. Tryptophan hydroxylase-2 knockout (Tph2-/-) mice exhibit sensitization of 5-HT1A agonist-induced inhibition of serotonergic neuron firing and thus represents a unique animal model of enhanced 5-HT1AAR functioning. To elucidate the mechanisms underlying 5-HT1AAR supersensitivity in Tph2-/- mice, we characterized the activation of G protein-coupled inwardly-rectifying potassium (GIRK) conductance by the 5-HT1A receptor agonist 5-carboxamidotryptamine using whole-cell recordings from serotonergic neurons in dorsal raphe nucleus. Tph2-/- mice exhibited a mean twofold leftward shift of the agonist concentration–response curve (p < 0.001) whereas the maximal response, proportional to the 5-HT1AAR number, was not