The Potassium Channel, Kir3.4 Participates in Angiotensin II-Stimulated Aldosterone Production by a Human Adrenocortical Cell Line

Oki, Kenji; Plonczynski, Maria W.; Lam, Milay Luis; Gómez-Sánchez, Elise P.; Gómez-Sánchez, Celso E.

doi:10.1210/en.2012-1241

Cited by 60 publications

(40 citation statements)

References 27 publications

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“…Overexpression of wild-type KCNJ5 in human adrenocortical cells was reported by Oki et al (382) ). Interestingly, however, in nontransfected human adrenal cells, administration of a GIRK inhibitor (tertiapin Q) had no effect on cell membrane current (263) and siRNA targeted KCNJ5 knockdown did not affect aldosterone production (382), suggesting that endogenously expressed KCNJ5 may be relatively inactive in normal ZG.…”

Section: F the "New" Genetics: Somatic And Germline Mutations In Genmentioning

confidence: 94%

Primary Aldosteronism: Changing Definitions and New Concepts of Physiology and Pathophysiology Both Inside and Outside the Kidney

Stowasser

Gordon

2016

Physiological Reviews

125

134

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In the 60 years that have passed since the discovery of the mineralocorticoid hormone aldosterone, much has been learned about its synthesis (both adrenal and extraadrenal), regulation (by renin-angiotensin II, potassium, adrenocorticotrophin, and other factors), and effects (on both epithelial and nonepithelial tissues). Once thought to be rare, primary aldosteronism (PA, in which aldosterone secretion by the adrenal is excessive and autonomous of its principal regulator, angiotensin II) is now known to be the most common specifically treatable and potentially curable form of hypertension, with most patients lacking the clinical feature of hypokalemia, the presence of which was previously considered to be necessary to warrant further efforts towards confirming a diagnosis of PA. This, and the appreciation that aldosterone excess leads to adverse cardiovascular, renal, central nervous, and psychological effects, that are at least partly independent of its effects on blood pressure, have had a profound influence on raising clinical and research interest in PA. Such research on patients with PA has, in turn, furthered knowledge regarding aldosterone synthesis, regulation, and effects. This review summarizes current progress in our understanding of the physiology of aldosterone, and towards defining the causes (including genetic bases), epidemiology, outcomes, and clinical approaches to diagnostic workup (including screening, diagnostic confirmation, and subtype differentiation) and treatment of PA.

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Section: F the "New" Genetics: Somatic And Germline Mutations In Genmentioning

confidence: 94%

Primary Aldosteronism: Changing Definitions and New Concepts of Physiology and Pathophysiology Both Inside and Outside the Kidney

Stowasser

Gordon

2016

Physiological Reviews

125

134

View full text Add to dashboard Cite

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“…Gomez-Sanchez (University of Mississippi Medical Center, Jackson, Mississippi, USA) (48). pLX303 KCNJ5 WT was generated from plx303 KCNJ5 G151R using a PCR-based strategy (QuikChange, Stratagene)…”

Section: Methodsmentioning

confidence: 99%

Macrolides selectively inhibit mutant KCNJ5 potassium channels that cause aldosterone-producing adenoma

Scholl

Abriola

Zhang

et al. 2017

Journal of Clinical Investigation

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tributed to cell maintenance. LA, UIS, and JSM designed and performed high-throughput screening assays. MP synthesized compounds. CZ and WW performed and analyzed electrophysiology. ENR performed qPCR analysis and ELISAs. UIS and BIK performed Kirby-Bauer disk-diffusion assays. UIS prepared figures and tables. UIS and RPL wrote and edited the main text and supplemental data. UIS, DH, JSM, WW, and RPL oversaw parts of the project or had advisory roles.

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“…Functional studies have demonstrated that GIRK4_Thr158Ala-transduced adrenocortical cells presented a loss in K C selectivity and greater influx of Na C into the cytoplasm resulting in the depolarization of the plasma membrane, thereby activating voltage-gated Ca 2C channels, leading to accumulation of intracellular Ca 2C . Increased intracellular Ca 2C activates the calcium signaling pathway resulting in the synthesis of steroidogenic enzymes and increased aldosterone production (Oki et al 2012b). Recent studies have described different germline KCNJ5 mutations in families with FH3.…”

Section: Familial Hyperaldosteronism Type IImentioning

confidence: 99%

An update on novel mechanisms of primary aldosteronism

Zennaro¹,

Boulkroun²,

Fernandes-Rosa³

2014

Journal of Endocrinology

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Primary aldosteronism (PA) is the most common and curable form of secondary hypertension. It is caused in the majority of cases by either unilateral aldosterone overproduction due to an aldosterone-producing adenoma (APA) or by bilateral adrenal hyperplasia. Recent advances in genome technology have allowed researchers to unravel part of the genetic abnormalities underlying the development of APA and familial hyperaldosteronism. Recurrent somatic mutations in genes coding for ion channels (KCNJ5 and CACNA1D) and ATPases (ATP1A1 and ATP2B3) regulating intracellular ionic homeostasis and cell membrane potential have been identified in APA. Similar germline mutations of KCNJ5 were identified in a severe familial form of PA, familial hyperaldosteronism type 3 (FH3), whereas de novo germline CACNA1D mutations were found in two cases of hyperaldosteronism associated with a complex neurological disorder. These results have allowed a pathophysiological model of APA development to be established. This model involves modifications in intracellular ionic homeostasis and membrane potential, accounting for w50% of all tumors, associated with specific gender differences and severity of PA. In this review, we describe the different genetic abnormalities associated with PA and discuss the mechanisms whereby they lead to increased aldosterone production and cell proliferation. We also address some of the foreseeable consequences that genetic knowledge may contribute to improve diagnosis and patient care.

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The Potassium Channel, Kir3.4 Participates in Angiotensin II-Stimulated Aldosterone Production by a Human Adrenocortical Cell Line

Cited by 60 publications

References 27 publications

Primary Aldosteronism: Changing Definitions and New Concepts of Physiology and Pathophysiology Both Inside and Outside the Kidney

Primary Aldosteronism: Changing Definitions and New Concepts of Physiology and Pathophysiology Both Inside and Outside the Kidney

Macrolides selectively inhibit mutant KCNJ5 potassium channels that cause aldosterone-producing adenoma

An update on novel mechanisms of primary aldosteronism

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