Tauber, P. and Penton, D. and Stindl, J. and Humberg, E. and Tegtmeier, I. and Sterner, C. and Beuschlein, F. and Reincke, M. and Barhanin, J. and Bandulik, S. and Warth, R. (2014) Pharmacology and Pathophysiology of Mutated KCNJ5 Found in Adrenal Aldosterone-Producing Adenomas. ENDOCRINOLOGY, 155 (4). pp. 1353-1362. ISSN 0013-7227, 1945-7170
Full text not available from this repository. (Request a copy)Abstract
Somatic mutations of the potassium channel KCNJ5 are found in 40% of aldosterone producing adenomas (APAs). APA-related mutations of KCNJ5 lead to a pathological Na+ permeability and a rise in cytosolic Ca2+, the latter presumably by depolarizing the membrane and activating voltage-gated Ca2+ channels. The aim of this study was to further investigate the effects of mutated KCNJ5 channels on intracellular Na+ and Ca2+ homeostasis in human adrenocortical NCI-H295R cells. Expression of mutant KCNJ5 led to a 2-fold increase in intracellular Na+ and, in parallel, to a substantial rise in intracellular Ca2+. The increase in Ca2+ appeared to be caused by activation of voltage-gated Ca2+ channels and by an impairment of Ca2+ extrusion by Na+/Ca2+ exchangers. The mutated KCNJ5 exhibited a pharmacological profile that differed from the one of wild-type channels. Mutated KCNJ5 was less Ba2+ and tertiapin-Q sensitive but was inhibited by blockers of Na+ and Ca2+-transporting proteins, such as verapamil and amiloride. The clinical use of these drugs might influence aldosterone levels in APA patients with KCNJ5 mutations. This might implicate diagnostic testing of APAs and could offer new therapeutic strategies.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | POTASSIUM CHANNEL; PRIMARY HYPERALDOSTERONISM; SOMATIC MUTATIONS; K+ CHANNELS; FAMILIAL HYPERALDOSTERONISM; CELL-LINE; LOW-RENIN; HYPERTENSION; ATP1A1; BIOSYNTHESIS; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Richard Warth |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Nov 2019 12:42 |
| Last Modified: | 14 Nov 2019 12:42 |
| URI: | https://pred.uni-regensburg.de/id/eprint/10331 |
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