Hypothalamic proopiomelanocortin neurons are glucose responsive and express K ATP channels

Autores
Ibrahim, Nurhadi; Bosch, Martha A.; Smart, James L.; Qiu, Jian; Rubinstein, Marcelo; Rønnekleiv, Oline K.; Low, Malcolm J.; Kelly, Martin J.
Año de publicación
2003
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Hypothalamic proopiomelanocortin (POMC) neurons are critical for controlling homeostatic functions in the mammal. We used a transgenic mouse model in which the POMC neurons were labeled with enhanced green fluorescent protein to perform visualized, whole-cell patch recordings from prepubertal female hypothalamic slices. The mouse POMC-enhanced green fluorescent protein neurons expressed the same endogenous conductances (a transient outward K + current and a hyperpolarization-activated, cation current) that have been described for guinea pig POMC neurons. In addition, the selective μ-opioid receptor agonist DAMGO induced an outward current (maximum of 12.8 ± 1.2 pA), which reversed at K + equilibrium potential (E K+ ), in the majority (85%) of POMC neurons with an EC 50 of 102 nM. This response was blocked by the opioid receptor antagonist naloxone with an inhibition constant of 3.1 nM. In addition, the γ-aminobutyric acid B receptor agonist baclofen (40 μM) caused an outward current (21.6 ± 4.0 pA) that reversed at E K+ in these same neurons. The ATP-sensitive potassium channel opener diazoxide also induced an outward K + current (maximum of 18.7 ± 2.2 pA) in the majority (92%) of POMC neurons with an EC 50 of 61 μM. The response to diazoxide was blocked by the sulfonylurea tolbutamide, indicating that the POMC neurons express both Kir6.2 and sulfonylurea receptor 1 channel subunits, which was verified using single cell RT-PCR. This pharmacological and molecular profile suggested that POMC neurons might be sensitive to metabolic inhibition, and indeed, we found that their firing rate varied with changes in glucose concentrations. Therefore, it appears that POMC neurons may function as an integrator of metabolic cues and synaptic input for controlling homeostasis in the mammal.
Fil: Ibrahim, Nurhadi. Oregon Health and Science University; Estados Unidos
Fil: Bosch, Martha A.. Oregon Health and Science University; Estados Unidos
Fil: Smart, James L.. Oregon Health and Science University; Estados Unidos
Fil: Qiu, Jian. Oregon Health and Science University; Estados Unidos
Fil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Rønnekleiv, Oline K.. Oregon Health and Science University; Estados Unidos
Fil: Low, Malcolm J.. Oregon Health and Science University; Estados Unidos
Fil: Kelly, Martin J.. Oregon Health and Science University; Estados Unidos
Materia
Glucosa
Neuronas
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/79855
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/79855
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Hypothalamic proopiomelanocortin neurons are glucose responsive and express K ATP channelsIbrahim, NurhadiBosch, Martha A.Smart, James L.Qiu, JianRubinstein, MarceloRønnekleiv, Oline K.Low, Malcolm J.Kelly, Martin J.GlucosaNeuronashttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Hypothalamic proopiomelanocortin (POMC) neurons are critical for controlling homeostatic functions in the mammal. We used a transgenic mouse model in which the POMC neurons were labeled with enhanced green fluorescent protein to perform visualized, whole-cell patch recordings from prepubertal female hypothalamic slices. The mouse POMC-enhanced green fluorescent protein neurons expressed the same endogenous conductances (a transient outward K + current and a hyperpolarization-activated, cation current) that have been described for guinea pig POMC neurons. In addition, the selective μ-opioid receptor agonist DAMGO induced an outward current (maximum of 12.8 ± 1.2 pA), which reversed at K + equilibrium potential (E K+ ), in the majority (85%) of POMC neurons with an EC 50 of 102 nM. This response was blocked by the opioid receptor antagonist naloxone with an inhibition constant of 3.1 nM. In addition, the γ-aminobutyric acid B receptor agonist baclofen (40 μM) caused an outward current (21.6 ± 4.0 pA) that reversed at E K+ in these same neurons. The ATP-sensitive potassium channel opener diazoxide also induced an outward K + current (maximum of 18.7 ± 2.2 pA) in the majority (92%) of POMC neurons with an EC 50 of 61 μM. The response to diazoxide was blocked by the sulfonylurea tolbutamide, indicating that the POMC neurons express both Kir6.2 and sulfonylurea receptor 1 channel subunits, which was verified using single cell RT-PCR. This pharmacological and molecular profile suggested that POMC neurons might be sensitive to metabolic inhibition, and indeed, we found that their firing rate varied with changes in glucose concentrations. Therefore, it appears that POMC neurons may function as an integrator of metabolic cues and synaptic input for controlling homeostasis in the mammal.Fil: Ibrahim, Nurhadi. Oregon Health and Science University; Estados UnidosFil: Bosch, Martha A.. Oregon Health and Science University; Estados UnidosFil: Smart, James L.. Oregon Health and Science University; Estados UnidosFil: Qiu, Jian. Oregon Health and Science University; Estados UnidosFil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Rønnekleiv, Oline K.. Oregon Health and Science University; Estados UnidosFil: Low, Malcolm J.. Oregon Health and Science University; Estados UnidosFil: Kelly, Martin J.. Oregon Health and Science University; Estados UnidosOxford University Press2003-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/79855Ibrahim, Nurhadi; Bosch, Martha A.; Smart, James L.; Qiu, Jian; Rubinstein, Marcelo; et al.; Hypothalamic proopiomelanocortin neurons are glucose responsive and express K ATP channels; Oxford University Press; Endocrinology; 144; 4; 4-2003; 1331-13400013-7227CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pubmed/12639916info:eu-repo/semantics/altIdentifier/doi/10.1210/en.2002-221033info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/endo/article/144/4/1331/2880620info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:38:03Zoai:ri.conicet.gov.ar:11336/79855instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 15:38:04.063CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Hypothalamic proopiomelanocortin neurons are glucose responsive and express K ATP channels
title Hypothalamic proopiomelanocortin neurons are glucose responsive and express K ATP channels
spellingShingle Hypothalamic proopiomelanocortin neurons are glucose responsive and express K ATP channels
Ibrahim, Nurhadi
Glucosa
Neuronas
title_short Hypothalamic proopiomelanocortin neurons are glucose responsive and express K ATP channels
title_full Hypothalamic proopiomelanocortin neurons are glucose responsive and express K ATP channels
title_fullStr Hypothalamic proopiomelanocortin neurons are glucose responsive and express K ATP channels
title_full_unstemmed Hypothalamic proopiomelanocortin neurons are glucose responsive and express K ATP channels
title_sort Hypothalamic proopiomelanocortin neurons are glucose responsive and express K ATP channels
dc.creator.none.fl_str_mv Ibrahim, Nurhadi
Bosch, Martha A.
Smart, James L.
Qiu, Jian
Rubinstein, Marcelo
Rønnekleiv, Oline K.
Low, Malcolm J.
Kelly, Martin J.
author Ibrahim, Nurhadi
author_facet Ibrahim, Nurhadi
Bosch, Martha A.
Smart, James L.
Qiu, Jian
Rubinstein, Marcelo
Rønnekleiv, Oline K.
Low, Malcolm J.
Kelly, Martin J.
author_role author
author2 Bosch, Martha A.
Smart, James L.
Qiu, Jian
Rubinstein, Marcelo
Rønnekleiv, Oline K.
Low, Malcolm J.
Kelly, Martin J.
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Glucosa
Neuronas
topic Glucosa
Neuronas
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Hypothalamic proopiomelanocortin (POMC) neurons are critical for controlling homeostatic functions in the mammal. We used a transgenic mouse model in which the POMC neurons were labeled with enhanced green fluorescent protein to perform visualized, whole-cell patch recordings from prepubertal female hypothalamic slices. The mouse POMC-enhanced green fluorescent protein neurons expressed the same endogenous conductances (a transient outward K + current and a hyperpolarization-activated, cation current) that have been described for guinea pig POMC neurons. In addition, the selective μ-opioid receptor agonist DAMGO induced an outward current (maximum of 12.8 ± 1.2 pA), which reversed at K + equilibrium potential (E K+ ), in the majority (85%) of POMC neurons with an EC 50 of 102 nM. This response was blocked by the opioid receptor antagonist naloxone with an inhibition constant of 3.1 nM. In addition, the γ-aminobutyric acid B receptor agonist baclofen (40 μM) caused an outward current (21.6 ± 4.0 pA) that reversed at E K+ in these same neurons. The ATP-sensitive potassium channel opener diazoxide also induced an outward K + current (maximum of 18.7 ± 2.2 pA) in the majority (92%) of POMC neurons with an EC 50 of 61 μM. The response to diazoxide was blocked by the sulfonylurea tolbutamide, indicating that the POMC neurons express both Kir6.2 and sulfonylurea receptor 1 channel subunits, which was verified using single cell RT-PCR. This pharmacological and molecular profile suggested that POMC neurons might be sensitive to metabolic inhibition, and indeed, we found that their firing rate varied with changes in glucose concentrations. Therefore, it appears that POMC neurons may function as an integrator of metabolic cues and synaptic input for controlling homeostasis in the mammal.
Fil: Ibrahim, Nurhadi. Oregon Health and Science University; Estados Unidos
Fil: Bosch, Martha A.. Oregon Health and Science University; Estados Unidos
Fil: Smart, James L.. Oregon Health and Science University; Estados Unidos
Fil: Qiu, Jian. Oregon Health and Science University; Estados Unidos
Fil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Rønnekleiv, Oline K.. Oregon Health and Science University; Estados Unidos
Fil: Low, Malcolm J.. Oregon Health and Science University; Estados Unidos
Fil: Kelly, Martin J.. Oregon Health and Science University; Estados Unidos
description Hypothalamic proopiomelanocortin (POMC) neurons are critical for controlling homeostatic functions in the mammal. We used a transgenic mouse model in which the POMC neurons were labeled with enhanced green fluorescent protein to perform visualized, whole-cell patch recordings from prepubertal female hypothalamic slices. The mouse POMC-enhanced green fluorescent protein neurons expressed the same endogenous conductances (a transient outward K + current and a hyperpolarization-activated, cation current) that have been described for guinea pig POMC neurons. In addition, the selective μ-opioid receptor agonist DAMGO induced an outward current (maximum of 12.8 ± 1.2 pA), which reversed at K + equilibrium potential (E K+ ), in the majority (85%) of POMC neurons with an EC 50 of 102 nM. This response was blocked by the opioid receptor antagonist naloxone with an inhibition constant of 3.1 nM. In addition, the γ-aminobutyric acid B receptor agonist baclofen (40 μM) caused an outward current (21.6 ± 4.0 pA) that reversed at E K+ in these same neurons. The ATP-sensitive potassium channel opener diazoxide also induced an outward K + current (maximum of 18.7 ± 2.2 pA) in the majority (92%) of POMC neurons with an EC 50 of 61 μM. The response to diazoxide was blocked by the sulfonylurea tolbutamide, indicating that the POMC neurons express both Kir6.2 and sulfonylurea receptor 1 channel subunits, which was verified using single cell RT-PCR. This pharmacological and molecular profile suggested that POMC neurons might be sensitive to metabolic inhibition, and indeed, we found that their firing rate varied with changes in glucose concentrations. Therefore, it appears that POMC neurons may function as an integrator of metabolic cues and synaptic input for controlling homeostasis in the mammal.
publishDate 2003
dc.date.none.fl_str_mv 2003-04
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/79855
Ibrahim, Nurhadi; Bosch, Martha A.; Smart, James L.; Qiu, Jian; Rubinstein, Marcelo; et al.; Hypothalamic proopiomelanocortin neurons are glucose responsive and express K ATP channels; Oxford University Press; Endocrinology; 144; 4; 4-2003; 1331-1340
0013-7227
CONICET Digital
CONICET
url http://hdl.handle.net/11336/79855
identifier_str_mv Ibrahim, Nurhadi; Bosch, Martha A.; Smart, James L.; Qiu, Jian; Rubinstein, Marcelo; et al.; Hypothalamic proopiomelanocortin neurons are glucose responsive and express K ATP channels; Oxford University Press; Endocrinology; 144; 4; 4-2003; 1331-1340
0013-7227
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pubmed/12639916
info:eu-repo/semantics/altIdentifier/doi/10.1210/en.2002-221033
info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/endo/article/144/4/1331/2880620
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.22299

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