Abnormalities in GABAA receptor structure and/or function have been associated with various forms of epilepsy in both humans and animals. Whether this is true for patients with gelastic seizures and hypothalamic hamartoma (HH) is unknown. In this study, we characterized the pharmacological properties and native subunit composition of GABAA receptors on acutely dissociated single neurons from surgically resected HH tissues using patch-clamp, immunocytochemical, and RT-PCR techniques. We found that 1) GABA induced an inward current (IGABA) at a holding potential of -60 mV; 2) IGABA was mimicked by the GABAA receptor agonist muscimol and blocked by the GABAA receptor antagonist bicuculline, suggesting that IGABA was mediated principally through the GABA A receptor; 3) the EC50 and Hill coefficient derived from the IGABA concentration-response curve were 6.8 μM and 1.9, respectively; 4) the current-voltage curve was linear at a reversal potential close to zero; and 5) IGABA exhibited low sensitivity to zinc and diazepam but higher sensitivity to pentobarbital and pregnanolone. Additionally, using Xenopus oocytes microtransplanted with normal human hypothalamic tissue, we confirmed that the functional properties of GABAA receptors were similar to those seen in small isolated HH neurons. Finally, the expression profile of GABAA receptor subunits obtained from normal control human hypothalamic tissue was identical to that from surgically resected human HH tissue. Taken together, our data indicate that GABAA receptors on small HH neurons exhibit normal pharmacosensitivity and subunit composition. These findings bear relevance to a broader understanding of inhibitory neurotransmission in human HH tissue.
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