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Electrophysiological properties of human hypothalamic hamartomas
Author(s) -
Wu Jie,
Xu Lin,
Kim Do Young,
Rho Jong M.,
John Paul A.,
Lue LihFen,
Coons Stephen,
Ellsworth Kevin,
Nowak Lee,
Johnson Eric,
Rekate Harold,
Kerrigan John F.
Publication year - 2005
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.20580
Subject(s) - electrophysiology , epileptogenesis , patch clamp , gabaergic , membrane potential , neuroscience , tetrodotoxin , glutamate receptor , hyperpolarization (physics) , current clamp , depolarization , inhibitory postsynaptic potential , biology , chemistry , endocrinology , epilepsy , biochemistry , receptor , organic chemistry , nuclear magnetic resonance spectroscopy
Abstract 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