TY - JOUR
T1 - Functional analysis of GABAA receptors in nucleus tractus solitarius neurons from neonatal rats
AU - Huang, Ren Qi
AU - Dillon, Glenn H.
N1 - Funding Information:
This work was supported by a grant from the American Heart Association.
Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 2001/12/7
Y1 - 2001/12/7
N2 - To gain insight into specific GABAA receptor configurations functionally expressed in the nucleus tractus solitarius (NTS), we conducted several physiological and pharmacological assessments. NTS neurons were characterized in thin brain slices from 1-14 day old rats using whole-cell patch clamp recordings. GABAA- receptor-mediated currents were detected in all neurons tested, with an average EC50 of 22.2 μM. GABA currents were consistently stimulated by diazepam (EC50=63 nM), zolpidem (EC50=85 nM), loreclezole (EC50=10.1 μM) and the neurosteroid 5α-pregnan-3α-hydroxy-20-one (3α-OH-DHP). In contrast, GABA-gated currents of the NTS were inhibited by the divalent cation Zn2+ (IC50=33.6 μM) picrotoxin (IC50=2.4 μM) and blockade of endogenous protein tyrosine kinase. GABA-activated currents were insensitive to furosemide (10-1000 μM) in all NTS neurons tested. Collectively, the data suggest that in neonatal rats, the predominant α subunit isoform present in GABAA receptors of the NTS appears to be the α1 and/or α2 subunit. β2 and/or β3 subunits are the major β isoform, while the predominant γ subunit is likely γ2. Our data suggest the contribution to NTS GABA currents by α3-α6, β1, γ1 and δ subunits, if present, is minor by comparison.
AB - To gain insight into specific GABAA receptor configurations functionally expressed in the nucleus tractus solitarius (NTS), we conducted several physiological and pharmacological assessments. NTS neurons were characterized in thin brain slices from 1-14 day old rats using whole-cell patch clamp recordings. GABAA- receptor-mediated currents were detected in all neurons tested, with an average EC50 of 22.2 μM. GABA currents were consistently stimulated by diazepam (EC50=63 nM), zolpidem (EC50=85 nM), loreclezole (EC50=10.1 μM) and the neurosteroid 5α-pregnan-3α-hydroxy-20-one (3α-OH-DHP). In contrast, GABA-gated currents of the NTS were inhibited by the divalent cation Zn2+ (IC50=33.6 μM) picrotoxin (IC50=2.4 μM) and blockade of endogenous protein tyrosine kinase. GABA-activated currents were insensitive to furosemide (10-1000 μM) in all NTS neurons tested. Collectively, the data suggest that in neonatal rats, the predominant α subunit isoform present in GABAA receptors of the NTS appears to be the α1 and/or α2 subunit. β2 and/or β3 subunits are the major β isoform, while the predominant γ subunit is likely γ2. Our data suggest the contribution to NTS GABA currents by α3-α6, β1, γ1 and δ subunits, if present, is minor by comparison.
KW - Brainstem
KW - GABA receptor
KW - Nucleus tractus solitarius
KW - Tyrosine kinase
UR - http://www.scopus.com/inward/record.url?scp=0035824291&partnerID=8YFLogxK
U2 - 10.1016/S0006-8993(01)03117-1
DO - 10.1016/S0006-8993(01)03117-1
M3 - Article
C2 - 11720725
AN - SCOPUS:0035824291
SN - 0006-8993
VL - 921
SP - 183
EP - 194
JO - Brain Research
JF - Brain Research
IS - 1-2
ER -