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Ann Neurol
2011 Apr 01;694:664-72. doi: 10.1002/ana.22298.
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Functional rundown of gamma-aminobutyric acid(A) receptors in human hypothalamic hamartomas.
Li G
,
Yang K
,
Zheng C
,
Liu Q
,
Chang Y
,
Kerrigan JF
,
Wu J
.
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Human hypothalamic hamartomas (HHs) are highly associated with treatment-resistant gelastic seizures. HHs are intrinsically epileptogenic, although the basic cellular mechanisms responsible for seizure activity are unknown. Altered gamma-aminobutyric acid (GABA) function can contribute to epileptogenesis in humans and animal models. Recently, functional GABA(A) receptor (GABA(A) R) rundown has been described in surgically resected human temporal lobe epilepsy tissue. We asked whether functional GABA(A) R rundown also occurs in human HH neurons. GABA(A) R-mediated currents were measured using perforated patch-clamp recordings in single neurons acutely dissociated from surgically resected HH tissue. In addition, functional GABA(A) Rs were expressed in Xenopus oocytes after microinjection with membrane fractions from either HH or control hypothalamus, and were studied with 2-electrode voltage-clamp recordings. Perforated patch-clamp recordings in dissociated HH neurons showed that repetitive exposure to GABA (5 consecutive exposures to 0.1 mM GABA with 1-second duration and at 20-second intervals) induced a time-dependent rundown of whole-cell currents in small HH neurons, whereas large HH neurons showed much less rundown using the same protocol. Functional rundown was not observed in HH neurons with repetitive exposure to glycine or glutamate. Two-electrode voltage-clamp recordings (6 consecutive exposures to 1 mM GABA with 10-second duration and at 40-second intervals) induced GABA current rundown in Xenopus oocytes microinjected with HH membrane proteins, but not in the oocytes expressing hypothalamic membrane proteins derived from human autopsy controls. Functional rundown of GABA currents was significantly attenuated by intracellular application of adenosine triphosphate or the nonspecific phosphatase inhibitor, okadaic acid. Neurons from surgically resected human HH demonstrate functional rundown of GABA(A) R-mediated transmembrane currents in response to GABA agonist exposure. Rundown may be a marker for impaired GABAergic function and a contributing mechanism for seizure genesis within HH tissue.
Andermann,
Hypothalamic hamartoma and epilepsy: the pathway of discovery.
2003, Pubmed
Andermann,
Hypothalamic hamartoma and epilepsy: the pathway of discovery.
2003,
Pubmed
Beggs,
Hypothalamic hamartomas associated with epilepsy: ultrastructural features.
2008,
Pubmed
Berkovic,
Human epileptogenesis and hypothalamic hamartomas: new lessons from an experiment of nature.
1997,
Pubmed
Berkovic,
Hypothalamic hamartomas and ictal laughter: evolution of a characteristic epileptic syndrome and diagnostic value of magnetic resonance imaging.
1988,
Pubmed
Boyko,
Hamartomas of the tuber cinereum: CT, MR, and pathologic findings.
1991,
Pubmed
Chen,
Phosphorylation of the retinoblastoma gene product is modulated during the cell cycle and cellular differentiation.
1989,
Pubmed
Chen,
GABAA receptor function is regulated by phosphorylation in acutely dissociated guinea-pig hippocampal neurones.
1990,
Pubmed
Coons,
The histopathology of hypothalamic hamartomas: study of 57 cases.
2007,
Pubmed
Culler,
Identification of gonadotropin-releasing hormone in neurons of a hypothalamic hamartoma in a boy with precocious puberty.
1985,
Pubmed
Deonna,
Hypothalamic hamartoma, precocious puberty and gelastic seizures: a special model of "epileptic" developmental disorder.
2000,
Pubmed
Diaz,
Hypothalamic hamartoma associated with Laurence-Moon-Biedl syndrome. Case report and review of the literature.
,
Pubmed
Diebler,
Hamartomas of the tuber cinereum.
1983,
Pubmed
Freeman,
The endocrinology of hypothalamic hamartoma surgery for intractable epilepsy.
2003,
Pubmed
Fukuda,
Stereotaxy for hypothalamic hamartoma with intractable gelastic seizures: technical case report.
1999,
Pubmed
Gyenes,
"Run-down" of gamma-aminobutyric acidA receptor function during whole-cell recording: a possible role for phosphorylation.
1988,
Pubmed
Gyenes,
Phosphorylation factors control neurotransmitter and neuromodulator actions at the gamma-aminobutyric acid type A receptor.
1994,
Pubmed
Harata,
Run-down of the GABAA response under experimental ischaemia in acutely dissociated CA1 pyramidal neurones of the rat.
1997,
Pubmed
Hochman,
Precocious puberty and hypothalamic hamartoma.
1981,
Pubmed
Hovinga,
Levetiracetam: a novel antiepileptic drug.
2001,
Pubmed
Huang,
Maintenance of recombinant type A gamma-aminobutyric acid receptor function: role of protein tyrosine phosphorylation and calcineurin.
1998,
Pubmed
Iannetti,
Gelastic epilepsy. A clinical contribution.
1992,
Pubmed
Jansen,
GABA(A) receptor properties in catastrophic infantile epilepsy.
2008,
Pubmed
,
Xenbase
Judge,
Hypothalamic hamartoma: a source of luteinizing-hormone-releasing factor in precocious puberty.
1977,
Pubmed
Kerrigan,
The hypothalamic hamartoma: a model of subcortical epileptogenesis and encephalopathy.
2005,
Pubmed
Kim,
Bicarbonate contributes to GABAA receptor-mediated neuronal excitation in surgically resected human hypothalamic hamartomas.
2009,
Pubmed
Kim,
GABAA receptor-mediated activation of L-type calcium channels induces neuronal excitation in surgically resected human hypothalamic hamartomas.
2008,
Pubmed
Kuzniecky,
Intrinsic epileptogenesis of hypothalamic hamartomas in gelastic epilepsy.
1997,
Pubmed
LIST,
Posterior hypothalamic hamartomas and gangliogliomas causing precocious puberty.
1958,
Pubmed
Laschet,
Dysfunction of GABAA receptor glycolysis-dependent modulation in human partial epilepsy.
2007,
Pubmed
Leal,
Interictal spike EEG source analysis in hypothalamic hamartoma epilepsy.
2002,
Pubmed
Levitan,
Modulation of ion channels by protein phosphorylation and dephosphorylation.
1994,
Pubmed
Maglóczky,
Impaired and repaired inhibitory circuits in the epileptic human hippocampus.
2005,
Pubmed
Miledi,
Microtransplantation of neurotransmitter receptors from cells to Xenopus oocyte membranes: new procedure for ion channel studies.
2006,
Pubmed
,
Xenbase
Mouginot,
Modulation of GABA-gated chloride currents by intracellular Ca2+ in cultured porcine melanotrophs.
1991,
Pubmed
Munari,
Role of the hypothalamic hamartoma in the genesis of gelastic fits (a video-stereo-EEG study).
1995,
Pubmed
Nash,
Levetiracetam.
2001,
Pubmed
Ng,
Transcallosal resection of hypothalamic hamartoma for intractable epilepsy.
2006,
Pubmed
Palma,
Phosphatase inhibitors remove the run-down of gamma-aminobutyric acid type A receptors in the human epileptic brain.
2004,
Pubmed
,
Xenbase
Palma,
Abnormal GABAA receptors from the human epileptic hippocampal subiculum microtransplanted to Xenopus oocytes.
2005,
Pubmed
,
Xenbase
Palma,
The antiepileptic drug levetiracetam stabilizes the human epileptic GABAA receptors upon repetitive activation.
2007,
Pubmed
,
Xenbase
Palma,
BDNF modulates GABAA receptors microtransplanted from the human epileptic brain to Xenopus oocytes.
2005,
Pubmed
,
Xenbase
Palmini,
Resection of the lesion in patients with hypothalamic hamartomas and catastrophic epilepsy.
2002,
Pubmed
Price,
Treatment of sexual precocity by removal of a luteinizing hormone-releasing hormone secreting hamartoma.
1984,
Pubmed
Ragozzino,
Rundown of GABA type A receptors is a dysfunction associated with human drug-resistant mesial temporal lobe epilepsy.
2005,
Pubmed
,
Xenbase
Rocamora,
Levetiracetam reduces frequency and duration of epileptic activity in patients with refractory primary generalized epilepsy.
2006,
Pubmed
Rosenfeld,
Transcallosal resection of hypothalamic hamartomas, with control of seizures, in children with gelastic epilepsy.
2001,
Pubmed
Shirasaki,
Direct modulation of GABAA receptor by intracellular ATP in dissociated nucleus tractus solitarii neurones of rat.
1992,
Pubmed
Sperk,
GABA and its receptors in epilepsy.
2004,
Pubmed
Stelzer,
GABAA-receptor function in hippocampal cells is maintained by phosphorylation factors.
1988,
Pubmed
Striano,
Functional changes in hypothalamic hamartoma neurons and gelastic epilepsy.
2011,
Pubmed
Terunuma,
Deficits in phosphorylation of GABA(A) receptors by intimately associated protein kinase C activity underlie compromised synaptic inhibition during status epilepticus.
2008,
Pubmed
Valdueza,
Hypothalamic hamartomas: with special reference to gelastic epilepsy and surgery.
1994,
Pubmed
Weissenberger,
Aggression and psychiatric comorbidity in children with hypothalamic hamartomas and their unaffected siblings.
2001,
Pubmed
Wu,
Electrophysiological properties and subunit composition of GABAA receptors in patients with gelastic seizures and hypothalamic hamartoma.
2007,
Pubmed
,
Xenbase
Wu,
Electrophysiological properties of human hypothalamic hamartomas.
2005,
Pubmed
Wu,
GABA(A) receptor-mediated excitation in dissociated neurons from human hypothalamic hamartomas.
2008,
Pubmed
