Journal article
Androgens block outward potassium currents and decrease spontaneous action potentials in GH(3) cells
Naunyn-Schmiedeberg's archives of pharmacology, v 388(1), pp 67-78
01 Jan 2015
PMID: 25344202
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Androgens produce nongenomic effects in several cells by different mechanisms, including ion channel modulation. Adenohypophyseal cells express several K+ channels, including voltage and Ca2+-dependent K+ (BK) channels, which might be the target of androgens to modulate cellular action potentials and hormonal secretion. Androgen effects were studied in GH(3) cells (from anterior pituitary rat tumor) by means of the patch-clamp technique. Cells were continuously perfused with saline solution, in the absence or presence of the androgens studied, while applying 40 mV pulses of 400 ms from a holding potential of -60 mV in whole-cell configuration with nystatin-perforated patches. Androgens reversibly blocked noninactivating K+ currents in a concentration-dependent manner without a latency period and with an order of efficacy of: 5 beta-dihydrotestosterone (DHT)> testosterone > 5 alpha-DHT. RT-PCR showed two isoforms of the alpha-pore forming subunits of BK channels. These channels are responsible for one third of the noninactivating current, according to the blockade of paxilline, a selective BK antagonist. Androgens seem to directly interact with BK channels since they were blocked in excised inside-out patches and independent of the whole-cell configuration and the NO-cGMP-dependent pathway. Testosterone, but not 5 alpha- or 5 beta-DHT, increased BK currents in HEK-293 cells overexpressing the short isoform, suggesting a cellular selectivity based on the alpha-subunits. The effect on noninactivating currents may be responsible for the decrease of spontaneous action potential frequency. Long-term cellular incubation with testosterone did not modify noninactivating currents density in GH(3) cells. It is remarkable that 5 beta-DHT, a reductase metabolite with weak androgenic activity, was the most efficient blocker.
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Details
- Title
- Androgens block outward potassium currents and decrease spontaneous action potentials in GH(3) cells
- Creators
- Lorena Suarez - Instituto de Investigación Sanitaria del Principado de AsturiasUsama Bilal - University of OviedoJavier Bordallo - University of OviedoBegona Cantabrana - University of OviedoManuel Sanchez - University of Oviedo
- Publication Details
- Naunyn-Schmiedeberg's archives of pharmacology, v 388(1), pp 67-78
- Publisher
- Springer Nature
- Number of pages
- 12
- Grant note
- Ministerio de Educacion, Spain; Spanish Government SV-UNOV-09-MA; SV-UNOV-10-MA2 / University of Oviedo, Spain Merck RL, Rahway, NJ, USA
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Urban Health Collaborative
- Web of Science ID
- WOS:000347406000008
- Scopus ID
- 2-s2.0-84922002756
- Other Identifier
- 991019189165704721
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- Web of Science research areas
- Pharmacology & Pharmacy