The Ca2+-activated, large conductance K+-channel (BKCa) is a player in the LH/hCG signaling cascade in testicular Leydig cells
In Leydig cells, hormonal stimulation by LH/hCG entails increased intracellular Ca2+ levels and steroid production, as well as hyperpolarization of the cell membrane. The large-conductance Ca2+-activated K+-channel (BKCa) is activated by raised intracellular Ca2+ and voltage and typically hyperpolar...
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todo:paper_03037207_v367_n1-2_p41_Matzkin2023-10-03T15:19:56Z The Ca2+-activated, large conductance K+-channel (BKCa) is a player in the LH/hCG signaling cascade in testicular Leydig cells Matzkin, M.E. Lauf, S. Spinnler, K. Rossi, S.P. Köhn, F.M. Kunz, L. Calandra, R.S. Frungieri, M.B. Mayerhofer, A. Ion channel Membrane potential StAR Testis Testosterone large conductance calcium activated potassium channel testosterone chorionic gonadotropin iberiotoxin KCNMA1 protein, human large conductance calcium activated potassium channel alpha subunit luteinizing hormone messenger RNA peptide phosphoprotein steroidogenic acute regulatory protein testosterone animal cell animal experiment animal tissue article biotinylation controlled study electrophysiology gene overexpression hamster hormone synthesis human human cell human tissue hyperpolarization immunohistochemistry immunoreactivity Leydig cell male membrane potential nonhuman ontogeny priority journal protein localization reverse transcription polymerase chain reaction signal transduction steroidogenesis animal biosynthesis cytology drug effect fluorescence gene expression regulation genetics metabolism Syrian hamster Animals Chorionic Gonadotropin Cricetinae Fluorescence Gene Expression Regulation Humans Large-Conductance Calcium-Activated Potassium Channel alpha Subunits Leydig Cells Luteinizing Hormone Male Membrane Potentials Mesocricetus Peptides Phosphoproteins RNA, Messenger Signal Transduction Testosterone In Leydig cells, hormonal stimulation by LH/hCG entails increased intracellular Ca2+ levels and steroid production, as well as hyperpolarization of the cell membrane. The large-conductance Ca2+-activated K+-channel (BKCa) is activated by raised intracellular Ca2+ and voltage and typically hyperpolarizes the cell membrane. Whether BKCa is functionally involved in steroid production of Leydig cells is not known. In order to explore this point we first investigated the localization of BKCa in human and hamster testes and then used a highly specific toxin, the BKCa blocker iberiotoxin (IbTx), to experimentally dissect a role of BKCa. Immunohistochemistry and RT-PCR revealed that adult Leydig cells of both species are endowed with these channels. Ontogeny studies in hamsters indicated that BKCa 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 BKCa 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 KV4-channels, expressed by Leydig cells, namely phrixotoxin-2 (PhTx-2) was not effective. In summary, the data reveal BKCa as a crucial part of the signaling cascade of LH/hCG in Leydig cells. The hyperpolarizing effect of BKCa in the Leydig cell membrane appears to set in motion events limiting the production of testosterone evoked by stimulatory endocrine mechanisms. © 2012 Elsevier Ireland Ltd. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_03037207_v367_n1-2_p41_Matzkin |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Ion channel Membrane potential StAR Testis Testosterone large conductance calcium activated potassium channel testosterone chorionic gonadotropin iberiotoxin KCNMA1 protein, human large conductance calcium activated potassium channel alpha subunit luteinizing hormone messenger RNA peptide phosphoprotein steroidogenic acute regulatory protein testosterone animal cell animal experiment animal tissue article biotinylation controlled study electrophysiology gene overexpression hamster hormone synthesis human human cell human tissue hyperpolarization immunohistochemistry immunoreactivity Leydig cell male membrane potential nonhuman ontogeny priority journal protein localization reverse transcription polymerase chain reaction signal transduction steroidogenesis animal biosynthesis cytology drug effect fluorescence gene expression regulation genetics metabolism Syrian hamster Animals Chorionic Gonadotropin Cricetinae Fluorescence Gene Expression Regulation Humans Large-Conductance Calcium-Activated Potassium Channel alpha Subunits Leydig Cells Luteinizing Hormone Male Membrane Potentials Mesocricetus Peptides Phosphoproteins RNA, Messenger Signal Transduction Testosterone |
| spellingShingle |
Ion channel Membrane potential StAR Testis Testosterone large conductance calcium activated potassium channel testosterone chorionic gonadotropin iberiotoxin KCNMA1 protein, human large conductance calcium activated potassium channel alpha subunit luteinizing hormone messenger RNA peptide phosphoprotein steroidogenic acute regulatory protein testosterone animal cell animal experiment animal tissue article biotinylation controlled study electrophysiology gene overexpression hamster hormone synthesis human human cell human tissue hyperpolarization immunohistochemistry immunoreactivity Leydig cell male membrane potential nonhuman ontogeny priority journal protein localization reverse transcription polymerase chain reaction signal transduction steroidogenesis animal biosynthesis cytology drug effect fluorescence gene expression regulation genetics metabolism Syrian hamster Animals Chorionic Gonadotropin Cricetinae Fluorescence Gene Expression Regulation Humans Large-Conductance Calcium-Activated Potassium Channel alpha Subunits Leydig Cells Luteinizing Hormone Male Membrane Potentials Mesocricetus Peptides Phosphoproteins RNA, Messenger Signal Transduction Testosterone Matzkin, M.E. Lauf, S. Spinnler, K. Rossi, S.P. Köhn, F.M. Kunz, L. Calandra, R.S. Frungieri, M.B. Mayerhofer, A. The Ca2+-activated, large conductance K+-channel (BKCa) is a player in the LH/hCG signaling cascade in testicular Leydig cells |
| topic_facet |
Ion channel Membrane potential StAR Testis Testosterone large conductance calcium activated potassium channel testosterone chorionic gonadotropin iberiotoxin KCNMA1 protein, human large conductance calcium activated potassium channel alpha subunit luteinizing hormone messenger RNA peptide phosphoprotein steroidogenic acute regulatory protein testosterone animal cell animal experiment animal tissue article biotinylation controlled study electrophysiology gene overexpression hamster hormone synthesis human human cell human tissue hyperpolarization immunohistochemistry immunoreactivity Leydig cell male membrane potential nonhuman ontogeny priority journal protein localization reverse transcription polymerase chain reaction signal transduction steroidogenesis animal biosynthesis cytology drug effect fluorescence gene expression regulation genetics metabolism Syrian hamster Animals Chorionic Gonadotropin Cricetinae Fluorescence Gene Expression Regulation Humans Large-Conductance Calcium-Activated Potassium Channel alpha Subunits Leydig Cells Luteinizing Hormone Male Membrane Potentials Mesocricetus Peptides Phosphoproteins RNA, Messenger Signal Transduction Testosterone |
| description |
In Leydig cells, hormonal stimulation by LH/hCG entails increased intracellular Ca2+ levels and steroid production, as well as hyperpolarization of the cell membrane. The large-conductance Ca2+-activated K+-channel (BKCa) is activated by raised intracellular Ca2+ and voltage and typically hyperpolarizes the cell membrane. Whether BKCa is functionally involved in steroid production of Leydig cells is not known. In order to explore this point we first investigated the localization of BKCa in human and hamster testes and then used a highly specific toxin, the BKCa blocker iberiotoxin (IbTx), to experimentally dissect a role of BKCa. Immunohistochemistry and RT-PCR revealed that adult Leydig cells of both species are endowed with these channels. Ontogeny studies in hamsters indicated that BKCa 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 BKCa 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 KV4-channels, expressed by Leydig cells, namely phrixotoxin-2 (PhTx-2) was not effective. In summary, the data reveal BKCa as a crucial part of the signaling cascade of LH/hCG in Leydig cells. The hyperpolarizing effect of BKCa in the Leydig cell membrane appears to set in motion events limiting the production of testosterone evoked by stimulatory endocrine mechanisms. © 2012 Elsevier Ireland Ltd. |
| format |
JOUR |
| author |
Matzkin, M.E. Lauf, S. Spinnler, K. Rossi, S.P. Köhn, F.M. Kunz, L. Calandra, R.S. Frungieri, M.B. Mayerhofer, A. |
| author_facet |
Matzkin, M.E. Lauf, S. Spinnler, K. Rossi, S.P. Köhn, F.M. Kunz, L. Calandra, R.S. Frungieri, M.B. Mayerhofer, A. |
| author_sort |
Matzkin, M.E. |
| title |
The Ca2+-activated, large conductance K+-channel (BKCa) is a player in the LH/hCG signaling cascade in testicular Leydig cells |
| 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 |
ca2+-activated, large conductance k+-channel (bkca) is a player in the lh/hcg signaling cascade in testicular leydig cells |
| url |
http://hdl.handle.net/20.500.12110/paper_03037207_v367_n1-2_p41_Matzkin |
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