The Journal of Neurophysiology Vol. 88 No. 4 October 2002, pp. 1655-1663
Copyright ©2002 by the American Physiological Society

Functional Characterization of GABA_A Receptors in Neonatal Hypothalamic Brain Slice

Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, Texas 76107

Huang, Ren-Qi and Glenn H. Dillon. Functional Characterization of GABA_A Receptors in Neonatal Hypothalamic Brain Slice. J. Neurophysiol. 88: 1655-1663, 2002. 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. GABA_A receptors are formed from a number of distinct subunits, designated , , , , , and , many of which have multiple isoforms. Little data exist, however, on the functional characteristics of the GABA_A receptors present on hypothalamic neurons. To gain insight into which GABA_A 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. GABA_A receptor-mediated currents were detected in all neurons tested and had an average EC₅₀ of 20 ± 1.6 µM. Hypothalamic GABA_A 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--carboline (EC₅₀ = 7.7 µM), and 5-pregnan-3-hydroxy-20-one (3-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 4/6-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 GABA_A receptor subtypes that incorporate 1 and/or 2 subunits, 2 and/or 3 subunits, and the 2 subunit. Our results suggest receptors expressing 3-6, 1, 1, and , if present, represent a minor component of functional hypothalamic GABA_A receptors.