ArticleAnnals of neurology2011
Functional rundown of gamma-aminobutyric acid(A) receptors in human hypothalamic hamartomas.
Article in Annals of neurology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 29 citations in OpenAlex.
- Multi-omics and electrophysiological examination of GABAMolecular psychiatry · 2026Article
- Direct energy consumption by inhibitory GABAFrontiers in neuroscience · 2026Article
- Massive Activation of GABABiomolecules · 2025Review
- Advances in epileptic network findings of hypothalamic hamartomas.Journal of central nervous system disease · 2024Review
- Physiological Role of ATPase for GABAInternational journal of molecular sciences · 2022Article
- Human iPSC Modeling of Genetic Febrile Seizure Reveals Aberrant Molecular and Physiological Features Underlying an Impaired Neuronal Activity.Biomedicines · 2022Article
- Dissecting the Molecular Determinants of GABABrain sciences · 2021Article
- Intricacies of GABAInternational journal of molecular sciences · 2021Review
- Hypothalamic hamartoma presenting with infantile spasms.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2017Article
- Activity-induced spontaneous spikes in GABAergic neurons suppress seizure discharges: an implication of computational modeling.Oncotarget · 2017Article
- Gap Junctions and Epileptogenesis: No Laughing Matter.EBioMedicine · 2016Article
- Mechanisms of intrinsic epileptogenesis in human gelastic seizures with hypothalamic hamartoma.CNS neuroscience & therapeutics · 2015Review
- Hyperactivation of BDNF-TrkB signaling cascades in human hypothalamic hamartoma (HH): a potential mechanism contributing to epileptogenesis.CNS neuroscience & therapeutics · 2015Article
- A portion of inhibitory neurons in human temporal lobe epilepsy are functionally upregulated: an endogenous mechanism for seizure termination.CNS neuroscience & therapeutics · 2015Article
- Firing behavior and network activity of single neurons in human epileptic hypothalamic hamartoma.Frontiers in neurology · 2013Article
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7 authors at 2 institutions in 1 country.
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Abstract
objectiveHuman 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.
methodsGABA(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.
resultsPerforated 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.
interpretationNeurons 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.
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