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

Do Young Kim; Kristina A. Fenoglio; John F. Kerrigan; Jong M. Rho

doi:10.1016/j.eplepsyres.2008.09.008

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

Do Young Kim, Kristina A. Fenoglio, John F. Kerrigan, Jong M. Rho

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Abstract

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

Original language	English (US)
Pages (from-to)	89-93
Number of pages	5
Journal	Epilepsy Research
Volume	83
Issue number	1
DOIs	https://doi.org/10.1016/j.eplepsyres.2008.09.008
State	Published - Jan 2009
Externally published	Yes

All Science Journal Classification (ASJC) codes

Neurology
Clinical Neurology

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10.1016/j.eplepsyres.2008.09.008

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@article{c46b584427ca4870b0b6a65ad5ab5855,

title = "Bicarbonate contributes to GABAA receptor-mediated neuronal excitation in surgically resected human hypothalamic hamartomas",

abstract = "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 (30 μM) provoked neuronal excitation in over 70% of large (18-22 μM) 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.",

author = "Kim, {Do Young} and Fenoglio, {Kristina A.} and Kerrigan, {John F.} and Rho, {Jong M.}",

note = "Funding Information: The authors wish to thank the patients and their families, and our pediatric neurosurgeon, Harold Rekate, for making this work possible. This work was supported by NIH grant NS 057786 and the Barrow Neurological Foundation.",

year = "2009",

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doi = "10.1016/j.eplepsyres.2008.09.008",

language = "English (US)",

volume = "83",

pages = "89--93",

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T1 - Bicarbonate contributes to GABAA receptor-mediated neuronal excitation in surgically resected human hypothalamic hamartomas

AU - Kim, Do Young

AU - Fenoglio, Kristina A.

AU - Kerrigan, John F.

AU - Rho, Jong M.

N1 - Funding Information: The authors wish to thank the patients and their families, and our pediatric neurosurgeon, Harold Rekate, for making this work possible. This work was supported by NIH grant NS 057786 and the Barrow Neurological Foundation.

PY - 2009/1

Y1 - 2009/1

N2 - 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 (30 μM) provoked neuronal excitation in over 70% of large (18-22 μM) 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.

AB - 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 (30 μM) provoked neuronal excitation in over 70% of large (18-22 μM) 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.

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

Abstract

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