TY - JOUR
T1 - Functional characterization of GABAA receptors in neonatal hypothalamic brain slice
AU - Huang, Ren Qi
AU - Dillon, Glenn H.
PY - 2002/10
Y1 - 2002/10
N2 - The hypothalamus influences a number of autonomic functions. The activity of hypothalamic neurons is modulated in part by release of the inhibitory neurotransmitter GABA onto these neurons. GABAA receptors are formed from a number of distinct subunits, designated α, β, γ, δ, ε, and θ, many of which have multiple isoforms. Little data exist, however, on the functional characteristics of the GABAA, receptors present on hypothalamic neurons. To gain insight into which GABAA receptor subunits are functionally expressed in the hypothalamus, we used an array of pharmacologic assessments. Whole cell recordings were made from thin hypothalamic slices obtained from 1- to 14-day-old rats. GABAA receptor-mediated currents were detected in all neurons tested and had an average EC50 of 20 ± 1.6 μM. Hypothalamic GABAA receptors were modulated by diazepam (EC50 = 0.060 μM), zolpidem (EC50 = 0.19 μM), loreclezole (EC50 = 4.4 μM), methyl-6,7-dimethoxy-4-ethyl-β-carboline (EC50 = 7.7 μM), and 5α-pregnan-3α-hydroxy-20-one (3α-OH-DHP). Conversely, these receptors were inhibited by Zn2+ (IC50 = 70.5 μM), dehydroepiandrosterone sulfate (IC50 = 16.7 μM), and picrotoxin (IC50 = 2.6 μM). The α4/6-selective antagonist furosemide (10-1,000 μM) was ineffective in all hypothalamic neurons tested. The results of our pharmacological analysis suggest that hypothalamic neurons express functional GABAA receptor subtypes that incorporate al and/or α2 subunits, β2 and/or β3 subunits, and the γ2 subunit. Our results suggest receptors expressing α3-α6, β1, γ1, and δ, if present, represent a minor component of functional hypothalamic GABAA receptors.
AB - The hypothalamus influences a number of autonomic functions. The activity of hypothalamic neurons is modulated in part by release of the inhibitory neurotransmitter GABA onto these neurons. GABAA receptors are formed from a number of distinct subunits, designated α, β, γ, δ, ε, and θ, many of which have multiple isoforms. Little data exist, however, on the functional characteristics of the GABAA, receptors present on hypothalamic neurons. To gain insight into which GABAA receptor subunits are functionally expressed in the hypothalamus, we used an array of pharmacologic assessments. Whole cell recordings were made from thin hypothalamic slices obtained from 1- to 14-day-old rats. GABAA receptor-mediated currents were detected in all neurons tested and had an average EC50 of 20 ± 1.6 μM. Hypothalamic GABAA receptors were modulated by diazepam (EC50 = 0.060 μM), zolpidem (EC50 = 0.19 μM), loreclezole (EC50 = 4.4 μM), methyl-6,7-dimethoxy-4-ethyl-β-carboline (EC50 = 7.7 μM), and 5α-pregnan-3α-hydroxy-20-one (3α-OH-DHP). Conversely, these receptors were inhibited by Zn2+ (IC50 = 70.5 μM), dehydroepiandrosterone sulfate (IC50 = 16.7 μM), and picrotoxin (IC50 = 2.6 μM). The α4/6-selective antagonist furosemide (10-1,000 μM) was ineffective in all hypothalamic neurons tested. The results of our pharmacological analysis suggest that hypothalamic neurons express functional GABAA receptor subtypes that incorporate al and/or α2 subunits, β2 and/or β3 subunits, and the γ2 subunit. Our results suggest receptors expressing α3-α6, β1, γ1, and δ, if present, represent a minor component of functional hypothalamic GABAA receptors.
UR - http://www.scopus.com/inward/record.url?scp=0036799586&partnerID=8YFLogxK
U2 - 10.1152/jn.2002.88.4.1655
DO - 10.1152/jn.2002.88.4.1655
M3 - Article
C2 - 12364495
AN - SCOPUS:0036799586
SN - 0022-3077
VL - 88
SP - 1655
EP - 1663
JO - Journal of neurophysiology
JF - Journal of neurophysiology
IS - 4
ER -