Bicarbonate contributes to GABA(A) receptor-mediated neuronal excitation in surgically resected human hypothalamic hamartomas

The role of bicarbonate (HCO3-) in GABA(A) receptor-mediated depolarization of human hypothalamic hamartoma (HH) neurons was investigated using cellular electrophysiological and calcium imaging techniques. Activation of GABA(A) receptors with muscimol (30 mu M) provoked neuronal excitation in over 70% of large (18-22 mu M) HH neurons in HCO3- buffer. Subsequent perfusion of HCO3--free HEPES buffer produced partial suppression of muscimol-induced excitation. Additionally, 53% of large HH neurons under HCO3--free conditions exhibited reduced intracellular calcium accumulation by muscimol. These results suggest that HCO3- efflux through GABA(A) receptors on a subpopulation of large HH neurons may contribute to membrane depolarization and subsequent activation of L-type calcium channels. (C) 2008 Elsevier B.V All rights reserved.