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" (2013) Molecular and Cellular Endocrinology. 367(1-2):41-49
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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.


Documento: Artículo
Título:The Ca2+-activated, large conductance K+-channel (BKCa) is a player in the LH/hCG signaling cascade in testicular Leydig cells
Autor:Matzkin, M.E.; Lauf, S.; Spinnler, K.; Rossi, S.P.; Köhn, F.M.; Kunz, L.; Calandra, R.S.; Frungieri, M.B.; Mayerhofer, A.
Filiación:Laboratorio de Esteroides, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires 1428, Argentina
Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires 1121, Argentina
Anatomy III - Cell Biology, University of Munich, D-80802 Munich, Germany
Andrologicum, D-80331 Munich, Germany
Neurobiology, Department Biology II, University of Munich, D-82152 Planegg-Martinsried, Germany
Palabras clave: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
Página de inicio:41
Página de fin:49
Título revista:Molecular and Cellular Endocrinology
Título revista abreviado:Mol. Cell. Endocrinol.
CAS:testosterone, 58-22-0; chorionic gonadotropin, 9002-61-3; iberiotoxin, 129203-60-7; luteinizing hormone, 39341-83-8, 9002-67-9; steroidogenic acute regulatory protein, 168183-61-7; Chorionic Gonadotropin; KCNMA1 protein, human; Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; Luteinizing Hormone, 9002-67-9; Peptides; Phosphoproteins; RNA, Messenger; Testosterone, 58-22-0; iberiotoxin, 129203-60-7; steroidogenic acute regulatory protein


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---------- APA ----------
Matzkin, M.E., Lauf, S., Spinnler, K., Rossi, S.P., Köhn, F.M., Kunz, L., Calandra, R.S.,..., Mayerhofer, A. (2013) . The Ca2+-activated, large conductance K+-channel (BKCa) is a player in the LH/hCG signaling cascade in testicular Leydig cells. Molecular and Cellular Endocrinology, 367(1-2), 41-49.
---------- CHICAGO ----------
Matzkin, M.E., Lauf, S., Spinnler, K., Rossi, S.P., Köhn, F.M., Kunz, L., et al. "The Ca2+-activated, large conductance K+-channel (BKCa) is a player in the LH/hCG signaling cascade in testicular Leydig cells" . Molecular and Cellular Endocrinology 367, no. 1-2 (2013) : 41-49.
---------- MLA ----------
Matzkin, M.E., Lauf, S., Spinnler, K., Rossi, S.P., Köhn, F.M., Kunz, L., et al. "The Ca2+-activated, large conductance K+-channel (BKCa) is a player in the LH/hCG signaling cascade in testicular Leydig cells" . Molecular and Cellular Endocrinology, vol. 367, no. 1-2, 2013, pp. 41-49.
---------- VANCOUVER ----------
Matzkin, M.E., Lauf, S., Spinnler, K., Rossi, S.P., Köhn, F.M., Kunz, L., et al. The Ca2+-activated, large conductance K+-channel (BKCa) is a player in the LH/hCG signaling cascade in testicular Leydig cells. Mol. Cell. Endocrinol. 2013;367(1-2):41-49.