Aldosterone up-regulates voltage-gated potassium currents and NKCC1 protein membrane fractions.

Autor: Bazard P; Department of Medical Engineering, College of Engineering, University of South Florida, Tampa, FL, 33620, USA.; Global Center for Hearing and Speech Research, University of South Florida, Tampa, FL, 33612, USA., Ding B; Department of Medical Engineering, College of Engineering, University of South Florida, Tampa, FL, 33620, USA.; Global Center for Hearing and Speech Research, University of South Florida, Tampa, FL, 33612, USA., Chittam HK; Department of Medical Engineering, College of Engineering, University of South Florida, Tampa, FL, 33620, USA.; Global Center for Hearing and Speech Research, University of South Florida, Tampa, FL, 33612, USA., Zhu X; Department of Medical Engineering, College of Engineering, University of South Florida, Tampa, FL, 33620, USA.; Global Center for Hearing and Speech Research, University of South Florida, Tampa, FL, 33612, USA., Parks TA; Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, FL, 33620, USA., Taylor-Clark TE; Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, FL, 33620, USA., Bhethanabotla VR; Department of Chemical Engineering, College of Engineering, University of South Florida, Tampa, FL, 33620, USA.; Global Center for Hearing and Speech Research, University of South Florida, Tampa, FL, 33612, USA., Frisina RD; Department of Medical Engineering, College of Engineering, University of South Florida, Tampa, FL, 33620, USA.; Department Communication Sciences and Disorders, College of Behavioral and Communication Sciences, Tampa, FL, 33620, USA.; Department of Chemical Engineering, College of Engineering, University of South Florida, Tampa, FL, 33620, USA.; Global Center for Hearing and Speech Research, University of South Florida, Tampa, FL, 33612, USA., Walton JP; Department of Medical Engineering, College of Engineering, University of South Florida, Tampa, FL, 33620, USA. jwalton1@usf.edu.; Department Communication Sciences and Disorders, College of Behavioral and Communication Sciences, Tampa, FL, 33620, USA. jwalton1@usf.edu.; Department of Chemical Engineering, College of Engineering, University of South Florida, Tampa, FL, 33620, USA. jwalton1@usf.edu.; Global Center for Hearing and Speech Research, University of South Florida, Tampa, FL, 33612, USA. jwalton1@usf.edu.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2020 Sep 24; Vol. 10 (1), pp. 15604. Date of Electronic Publication: 2020 Sep 24.
DOI: 10.1038/s41598-020-72450-4
Abstrakt: Na + -K + -2Cl - Cotransporter (NKCC1) is a protein that aids in the active transport of sodium, potassium, and chloride ions across cell membranes. It has been shown that long-term systemic treatment with aldosterone (ALD) can enhance NKCC1 protein expression and activity in the aging cochlea resulting in improved hearing. In the present work, we used a cell line with confirmed NKCC1 expression to demonstrate that in vitro application of ALD increased outward voltage-gated potassium currents significantly, and simultaneously upregulated whole lysate and membrane portion NKCC1 protein expression. These ALD-induced changes were blocked by applying the mineralocorticoid receptor antagonist eplerenone. However, application of the NKCC1 inhibitor bumetanide or the potassium channel antagonist Tetraethyl ammonium had no effect. In addition, NKKC1 mRNA levels remained stable, indicating that ALD modulates NKCC1 protein expression via the activation of mineralocorticoid receptors and post-transcriptional modifications. Further, in vitro electrophysiology experiments, with ALD in the presence of NKCC1, K + channel and mineralocorticoid receptor inhibitors, revealed interactions between NKCC1 and outward K + channels, mediated by a mineralocorticoid receptor-ALD complex. These results provide evidence of the therapeutic potential of ALD for the prevention/treatment of inner ear disorders such as age-related hearing loss.
Databáze: MEDLINE
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