The Ca2+-activated, large conductance K+ channel (BKCa) is a player in the LH/hCG signaling cascade in testicular Leydig cells.

Autores
Matzkin, Maria Eugenia; Lauf, S.; Spinnler, K.; Rossi, Soledad Paola; Köhn, F.; Kunz, L.; Calandra, Ricardo Saul; Frungieri, Monica Beatriz; Mayerhofer, A.
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
In Leydig cells, hormonal stimulation by LH/hCG entails increased intracellular Ca(2+) levels and steroid production, as well as hyperpolarization of the cell membrane. The large-conductance Ca(2+)-activated K(+)-channel (BK(Ca)) is activated by raised intracellular Ca(2+) and voltage and typically hyperpolarizes the cell membrane. Whether BK(Ca) is functionally involved in steroid production of Leydig cells is not known. In order to explore this point we first investigated the localization of BK(Ca) in human and hamster testes and then used a highly specific toxin, the BK(Ca) blocker iberiotoxin (IbTx), to experimentally dissect a role of BK(Ca). Immunohistochemistry and RT-PCR revealed that adult Leydig cells of both species are endowed with these channels. Ontogeny studies in hamsters indicated that BK(Ca) becomes strongly detectable in Leydig cells only after they acquire the ability to produce androgens. Using purified Leydig cells from adult hamsters, membrane potential changes in response to hCG were monitored. HCG hyperpolarized the cell membrane, which was prevented by the selective BK(Ca) blocker IbTx. Steroidogenic acute regulatory (StAR) mRNA expression and testosterone production were not affected by IbTx under basal conditions but markedly increased when hCG, in submaximal and maximal concentration or when db-cAMP was added to the incubation media. A blocker of K(V)4-channels, expressed by Leydig cells, namely phrixotoxin-2 (PhTx-2) was not effective. In summary, the data reveal BK(Ca) as a crucial part of the signaling cascade of LH/hCG in Leydig cells. The hyperpolarizing effect of BK(Ca) in the Leydig cell membrane appears to set in motion events limiting the production of testosterone evoked by stimulatory endocrine mechanisms.
Fil: Matzkin, Maria Eugenia. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Lauf, S.. University of Munich. Anatomy III. Cell Biology; Alemania
Fil: Spinnler, K.. University of Munich. Anatomy III. Cell Biology; Alemania
Fil: Rossi, Soledad Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina
Fil: Köhn, F.. Andrologicum; Alemania
Fil: Kunz, L.. University of Munich. Department Biology II. Neurobiology; Alemania
Fil: Calandra, Ricardo Saul. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Frungieri, Monica Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina
Fil: Mayerhofer, A.. University of Munich. Cell Biology; Alemania
Materia
Ion Channel
Testis
Membrane Potential
Testosterone
Star
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/2620
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/2620
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling The Ca2+-activated, large conductance K+ channel (BKCa) is a player in the LH/hCG signaling cascade in testicular Leydig cells.Matzkin, Maria EugeniaLauf, S.Spinnler, K.Rossi, Soledad PaolaKöhn, F.Kunz, L.Calandra, Ricardo SaulFrungieri, Monica BeatrizMayerhofer, A.Ion ChannelTestisMembrane PotentialTestosteroneStarhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3In Leydig cells, hormonal stimulation by LH/hCG entails increased intracellular Ca(2+) levels and steroid production, as well as hyperpolarization of the cell membrane. The large-conductance Ca(2+)-activated K(+)-channel (BK(Ca)) is activated by raised intracellular Ca(2+) and voltage and typically hyperpolarizes the cell membrane. Whether BK(Ca) is functionally involved in steroid production of Leydig cells is not known. In order to explore this point we first investigated the localization of BK(Ca) in human and hamster testes and then used a highly specific toxin, the BK(Ca) blocker iberiotoxin (IbTx), to experimentally dissect a role of BK(Ca). Immunohistochemistry and RT-PCR revealed that adult Leydig cells of both species are endowed with these channels. Ontogeny studies in hamsters indicated that BK(Ca) becomes strongly detectable in Leydig cells only after they acquire the ability to produce androgens. Using purified Leydig cells from adult hamsters, membrane potential changes in response to hCG were monitored. HCG hyperpolarized the cell membrane, which was prevented by the selective BK(Ca) blocker IbTx. Steroidogenic acute regulatory (StAR) mRNA expression and testosterone production were not affected by IbTx under basal conditions but markedly increased when hCG, in submaximal and maximal concentration or when db-cAMP was added to the incubation media. A blocker of K(V)4-channels, expressed by Leydig cells, namely phrixotoxin-2 (PhTx-2) was not effective. In summary, the data reveal BK(Ca) as a crucial part of the signaling cascade of LH/hCG in Leydig cells. The hyperpolarizing effect of BK(Ca) in the Leydig cell membrane appears to set in motion events limiting the production of testosterone evoked by stimulatory endocrine mechanisms.Fil: Matzkin, Maria Eugenia. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Lauf, S.. University of Munich. Anatomy III. Cell Biology; AlemaniaFil: Spinnler, K.. University of Munich. Anatomy III. Cell Biology; AlemaniaFil: Rossi, Soledad Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Köhn, F.. Andrologicum; AlemaniaFil: Kunz, L.. University of Munich. Department Biology II. Neurobiology; AlemaniaFil: Calandra, Ricardo Saul. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Frungieri, Monica Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Mayerhofer, A.. University of Munich. Cell Biology; AlemaniaElsevier Ireland2013-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/2620Matzkin, Maria Eugenia; Lauf, S.; Spinnler, K.; Rossi, Soledad Paola; Köhn, F.; et al.; The Ca2+-activated, large conductance K+ channel (BKCa) is a player in the LH/hCG signaling cascade in testicular Leydig cells.; Elsevier Ireland; Molecular And Cellular Endocrinology; 367; 1-2; 3-2013; 41-490303-72071872-8057enginfo:eu-repo/semantics/altIdentifier/ark/10.1016/j.mce.2012.12.015info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0303720712005394info:eu-repo/semantics/altIdentifier/doi/10.1016/j.mce.2012.12.015info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:10:35Zoai:ri.conicet.gov.ar:11336/2620instacron: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:34982025-09-03 10:10:35.977CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The Ca2+-activated, large conductance K+ channel (BKCa) is a player in the LH/hCG signaling cascade in testicular Leydig cells.
title The Ca2+-activated, large conductance K+ channel (BKCa) is a player in the LH/hCG signaling cascade in testicular Leydig cells.
spellingShingle The Ca2+-activated, large conductance K+ channel (BKCa) is a player in the LH/hCG signaling cascade in testicular Leydig cells.
Matzkin, Maria Eugenia
Ion Channel
Testis
Membrane Potential
Testosterone
Star
title_short The Ca2+-activated, large conductance K+ channel (BKCa) is a player in the LH/hCG signaling cascade in testicular Leydig cells.
title_full The Ca2+-activated, large conductance K+ channel (BKCa) is a player in the LH/hCG signaling cascade in testicular Leydig cells.
title_fullStr The Ca2+-activated, large conductance K+ channel (BKCa) is a player in the LH/hCG signaling cascade in testicular Leydig cells.
title_full_unstemmed The Ca2+-activated, large conductance K+ channel (BKCa) is a player in the LH/hCG signaling cascade in testicular Leydig cells.
title_sort The Ca2+-activated, large conductance K+ channel (BKCa) is a player in the LH/hCG signaling cascade in testicular Leydig cells.
dc.creator.none.fl_str_mv Matzkin, Maria Eugenia
Lauf, S.
Spinnler, K.
Rossi, Soledad Paola
Köhn, F.
Kunz, L.
Calandra, Ricardo Saul
Frungieri, Monica Beatriz
Mayerhofer, A.
author Matzkin, Maria Eugenia
author_facet Matzkin, Maria Eugenia
Lauf, S.
Spinnler, K.
Rossi, Soledad Paola
Köhn, F.
Kunz, L.
Calandra, Ricardo Saul
Frungieri, Monica Beatriz
Mayerhofer, A.
author_role author
author2 Lauf, S.
Spinnler, K.
Rossi, Soledad Paola
Köhn, F.
Kunz, L.
Calandra, Ricardo Saul
Frungieri, Monica Beatriz
Mayerhofer, A.
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Ion Channel
Testis
Membrane Potential
Testosterone
Star
topic Ion Channel
Testis
Membrane Potential
Testosterone
Star
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv In Leydig cells, hormonal stimulation by LH/hCG entails increased intracellular Ca(2+) levels and steroid production, as well as hyperpolarization of the cell membrane. The large-conductance Ca(2+)-activated K(+)-channel (BK(Ca)) is activated by raised intracellular Ca(2+) and voltage and typically hyperpolarizes the cell membrane. Whether BK(Ca) is functionally involved in steroid production of Leydig cells is not known. In order to explore this point we first investigated the localization of BK(Ca) in human and hamster testes and then used a highly specific toxin, the BK(Ca) blocker iberiotoxin (IbTx), to experimentally dissect a role of BK(Ca). Immunohistochemistry and RT-PCR revealed that adult Leydig cells of both species are endowed with these channels. Ontogeny studies in hamsters indicated that BK(Ca) becomes strongly detectable in Leydig cells only after they acquire the ability to produce androgens. Using purified Leydig cells from adult hamsters, membrane potential changes in response to hCG were monitored. HCG hyperpolarized the cell membrane, which was prevented by the selective BK(Ca) blocker IbTx. Steroidogenic acute regulatory (StAR) mRNA expression and testosterone production were not affected by IbTx under basal conditions but markedly increased when hCG, in submaximal and maximal concentration or when db-cAMP was added to the incubation media. A blocker of K(V)4-channels, expressed by Leydig cells, namely phrixotoxin-2 (PhTx-2) was not effective. In summary, the data reveal BK(Ca) as a crucial part of the signaling cascade of LH/hCG in Leydig cells. The hyperpolarizing effect of BK(Ca) in the Leydig cell membrane appears to set in motion events limiting the production of testosterone evoked by stimulatory endocrine mechanisms.
Fil: Matzkin, Maria Eugenia. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Lauf, S.. University of Munich. Anatomy III. Cell Biology; Alemania
Fil: Spinnler, K.. University of Munich. Anatomy III. Cell Biology; Alemania
Fil: Rossi, Soledad Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina
Fil: Köhn, F.. Andrologicum; Alemania
Fil: Kunz, L.. University of Munich. Department Biology II. Neurobiology; Alemania
Fil: Calandra, Ricardo Saul. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Frungieri, Monica Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina
Fil: Mayerhofer, A.. University of Munich. Cell Biology; Alemania
description In Leydig cells, hormonal stimulation by LH/hCG entails increased intracellular Ca(2+) levels and steroid production, as well as hyperpolarization of the cell membrane. The large-conductance Ca(2+)-activated K(+)-channel (BK(Ca)) is activated by raised intracellular Ca(2+) and voltage and typically hyperpolarizes the cell membrane. Whether BK(Ca) is functionally involved in steroid production of Leydig cells is not known. In order to explore this point we first investigated the localization of BK(Ca) in human and hamster testes and then used a highly specific toxin, the BK(Ca) blocker iberiotoxin (IbTx), to experimentally dissect a role of BK(Ca). Immunohistochemistry and RT-PCR revealed that adult Leydig cells of both species are endowed with these channels. Ontogeny studies in hamsters indicated that BK(Ca) becomes strongly detectable in Leydig cells only after they acquire the ability to produce androgens. Using purified Leydig cells from adult hamsters, membrane potential changes in response to hCG were monitored. HCG hyperpolarized the cell membrane, which was prevented by the selective BK(Ca) blocker IbTx. Steroidogenic acute regulatory (StAR) mRNA expression and testosterone production were not affected by IbTx under basal conditions but markedly increased when hCG, in submaximal and maximal concentration or when db-cAMP was added to the incubation media. A blocker of K(V)4-channels, expressed by Leydig cells, namely phrixotoxin-2 (PhTx-2) was not effective. In summary, the data reveal BK(Ca) as a crucial part of the signaling cascade of LH/hCG in Leydig cells. The hyperpolarizing effect of BK(Ca) in the Leydig cell membrane appears to set in motion events limiting the production of testosterone evoked by stimulatory endocrine mechanisms.
publishDate 2013
dc.date.none.fl_str_mv 2013-03
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/11336/2620
Matzkin, Maria Eugenia; Lauf, S.; Spinnler, K.; Rossi, Soledad Paola; Köhn, F.; et al.; The Ca2+-activated, large conductance K+ channel (BKCa) is a player in the LH/hCG signaling cascade in testicular Leydig cells.; Elsevier Ireland; Molecular And Cellular Endocrinology; 367; 1-2; 3-2013; 41-49
0303-7207
1872-8057
url http://hdl.handle.net/11336/2620
identifier_str_mv Matzkin, Maria Eugenia; Lauf, S.; Spinnler, K.; Rossi, Soledad Paola; Köhn, F.; et al.; The Ca2+-activated, large conductance K+ channel (BKCa) is a player in the LH/hCG signaling cascade in testicular Leydig cells.; Elsevier Ireland; Molecular And Cellular Endocrinology; 367; 1-2; 3-2013; 41-49
0303-7207
1872-8057
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/ark/10.1016/j.mce.2012.12.015
info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0303720712005394
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.mce.2012.12.015
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Ireland
publisher.none.fl_str_mv Elsevier Ireland
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 13.13397

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