Developmental changes in GABA(A) tonic inhibition are compromised by multiple mechanisms in preadolescent dentate gyrus granule cells

作者：Pandit Sudip; Lee Gyu Seung; Park Jin Bong^*

来源：Korean Journal of Physiology and Pharmacology, 2017, 21(6): 695-702.

DOI：10.4196/kjpp.2017.21.6.695

• Ages
• Dentate gyrus granule cells
• Extrasynaptic GABA(A) receptors
• GABA transporter

The sustained tonic currents (l(tonic)) generated by gamma-aminobutyric acid A receptors (GABA(A)Rs) are implicated in diverse age-dependent brain functions. While various mechanisms regulating l(tonic) in the hippocampus are known, their combined role in regulation not well understood in different age groups. In this study, we demonstrated that developmental increase in GABA transporter GAT) expression, combined with gradual decrease in GABAAR a, subunit, resulted in various l(tonic) in the dentate gyrus granule cells (DGGCs) of preadolescent rats. Both GAT-1 and GAT3 expression gradually increased at infantile (P6-8 and P13-15) and juvenile (P20-22 and P27-29) stages, with stabilization observed thereafter in adolescents (P3-36) and young adults (P4-13) I-tonic facilitation of a selective GAT-1 blocker (NO-711) was significantly less negligible in the absence of exogenous GABA at all tested ages. In contrast, I-tonic in the presence of a nonselective GAT blocker (nipecotic acid, NPA) gradually decreased ' with age during the preadolescent period, which was mimicked by l(tonic) changes in the presence of exogenous GABA. Ionic sensitivity L-655,708, GAB(A)AR alpha(s), subunit inverse agonist, gradually decreased during the preadolescent period in the presence of NPA or exogenous GABA. Finally, Western blot analysis showed that the expression the GABA(A)R(alpha) subunit in the dentate gyrus gradually decreased with age. Collectively, our results suggested that the l(tonic), regulation of altered GATs is under the final tune of GABAAR a, subunit activation in DGGCs at different ages.

• 出版日期2017-11