Bicarbonate contributes to GABAA receptor-mediated neuronal excitation in surgically resected human hypothalamic hamartomas

The role of bicarbonate (HCO3−) in GABAA receptor-mediated depolarization of human hypothalamic hamartoma (HH) neurons was investigated using cellular electrophysiological and calcium imaging techniques. Activation of GABAA receptors with muscimol (30μM) provoked neuronal excitation in over 70% of large (18–22μM) 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 GABAA receptors on a subpopulation of large HH neurons may contribute to membrane depolarization and subsequent activation of L-type calcium channels.