Alpha2-adrenergic mediation of membrane potential changes in medial prefrontal cortex (mPFC) pyramidal neurons in young rats

• Autorzy: Grzelka K. , Szulczyk P.
• Języki publikacji: EN

Abstrakty

EN

BACKGROUD AND AIMS: Impairment of the signal transduction from adrenergic receptors to cellular effectors in prefrontal cortex (PFC) neurons occurs in many neuropsychiatric disorders (acute stress disorder, ADHD). Application of clonidine (α2-adrenergic receptor agonist) evokes hyperpolarisation of the resting membrane potential in mPFC pyramidal neurons. The aim of the study was to define the cellular effectors and the exact signal transduction pathway from the receptor to the effector, which still remains unclear. METHODS: The membrane potential was recorded in layer V mPFC pyramidal neurons in slices isolated from 3-week-old rats. Recordings were performed in perforated-patch configuration at a temperature of 34°C. Adrenergic antagonists, inhibitors of cellular effectors and intracellular signalling were applied to the bath medium before, during and after clonidine application (100 µM). Their effects on clonidine-dependent membrane potential changes were analysed. RESULTS: The α2-receptor antagonists yohimbine (60 µM, n=15) and atipamezole (20 µM, n=6) did not completely block clonidinedependent hyperpolarisation. The effect of clonidine was attenuated by the blocker of hyperpolarisation-activated cyclic nucleotide-gated (HCN) channels (ZD7288, 50 µM, n=10) and by the selective Na+ / K+ -ATPase inhibitor (ouabain, 100 µM, n=7). The hyperpolarisation was affected neither by the adenylyl cyclase inhibitor (SQ22536, 100 µM, n=6), protein kinase A inhibitor (H-89, 40 µM, n=6), phospholipase C inhibitor (U73122, 10 µM, n=7) nor the protein kinase C inhibitor (chelerythrine, 5 µM, n=5), but it was attenuated by the G-protein βγ-subunit inhibitor (gallein, 20 µM, n=12). CONCLUSIONS: α2-Adrenergic receptor activation evokes hyperpolarisation due to HCN channel inhibition and modification of the Na+ /K+ -ATPase function. The transduction pathway occurs in a membrane-delimited fashion and involves the Gβγ subunit released from the G-protein. Supported by grants no: NN401584638 and NN301572940.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2015
• Tom: 75
• Numer: Supl.
• Opis fizyczny: p.S43

Twórcy

autor

Grzelka K.

• Medical University of Warsaw, Warsaw, Poland

autor

Szulczyk P.

• Medical University of Warsaw, Warsaw, Poland