Electrophysiological properties of human hypothalamic hamartomas

• Published in: Annals of neurology 2005-09, Vol.58 (3), p.371-382
• Main Authors: Wu, Jie, Xu, Lin, Kim, Do Young, Rho, Jong M., John, Paul A., Lue, Lih‐Fen, Coons, Stephen, Ellsworth, Kevin, Nowak, Lee, Johnson, Eric, Rekate, Harold, Kerrigan, John F.
• Format: Article
• Language: English
• Subjects: 6-Cyano-7-nitroquinoxaline-2,3-dione - pharmacology; Adolescent; Adult; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid - pharmacology; Anesthetics, Local - pharmacology; Bicuculline - analogs & derivatives; Bicuculline - pharmacology; Cadmium Chloride - pharmacology; Child; Child, Preschool; Drug Interactions; Electrophysiology; Excitatory Amino Acid Agonists - pharmacology; Excitatory Amino Acid Antagonists - pharmacology; Female; GABA Antagonists - pharmacology; gamma-Aminobutyric Acid - pharmacology; Glial Fibrillary Acidic Protein - metabolism; Glutamate Decarboxylase - metabolism; Glutamic Acid - pharmacology; Hamartoma - metabolism; Hamartoma - pathology; Hamartoma - physiopathology; Hamartoma - surgery; Humans; Hypothalamus - metabolism; Hypothalamus - pathology; Hypothalamus - physiopathology; Hypothalamus - surgery; Immunohistochemistry - methods; In Vitro Techniques; Infant; Isoenzymes - metabolism; Kainic Acid - pharmacology; Male; Membrane Potentials - physiology; Neurons - classification; Neurons - metabolism; Neurons - physiology; Patch-Clamp Techniques - methods; Periodicity; Phosphopyruvate Hydratase - metabolism; Potassium Channel Blockers - pharmacology; Tetraethylammonium - pharmacology; Tetrodotoxin - pharmacology; Valine - analogs & derivatives; Valine - pharmacology
• ISSN: 0364-5134; 1531-8249
• DOI: 10.1002/ana.20580

The hypothalamic hamartoma (HH) is a rare developmental malformation often characterized by gelastic seizures, which are usually refractory to medical therapy. The mechanisms of epileptogenesis operative in this subcortical lesion are unknown. In this study, we used standard patch‐clamp electrophysiological techniques combined with histochemical approaches to study individual cells from human HH tissue immediately after surgical resection. More than 90% of dissociated HH cells were small (6–9μm soma) and exhibited immunoreactivity to the neuronal marker NeuN, and to glutamic acid decarboxylase, but not to glial fibrillary acidic protein. Under current‐clamp, whole‐cell recordings in single dissociated cells or in intact HH slices demonstrated typical neuronal responses to depolarizing and hyperpolarizing current injection. In some cases, HH cells exhibited a “sag‐like” membrane potential change during membrane hyperpolarization. Interestingly, most HH cells exhibited robust, spontaneous “pacemaker‐like” action potential firing. Under voltage‐clamp, dissociated HH cells exhibited functional tetrodotoxin (TTX)–sensitive Na+ and tetraethylammonium‐sensitive K+ currents. Both GABA and glutamate evoked whole‐cell currents, with GABA exhibiting a peak current amplitude 10‐fold greater than glutamate. These findings suggest that human HH tissues, associated with gelastic seizures, contained predominantly small GABAergic inhibitory neurons that exhibited intrinsic “pacemaker‐like” behavior. Ann Neurol 2005;58:371–382