title: Of channels and pumps: different ways to boost the aldosterone?
abstract: The mineralocorticoid aldosterone is a major factor controlling the salt and water balance and thereby also the arterial blood pressure. Accordingly, primary aldosteronism (PA) characterized by an inappropriately high aldosterone secretion is the most common form of secondary hypertension. The physiological stimulation of aldosterone synthesis in adrenocortical glomerulosa cells by angiotensin II and an increased plasma K+concentration depends on a membrane depolarization and an increase in the cytosolic Ca2+activity. Recurrent gain-of-function mutations of ion channels and transporters have been identified in a majority of cases of aldosterone-producing adenomas and in familial forms of PA. In this review, the physiological role of these genes in the regulation of aldosterone synthesis and the altered function of the mutant proteins as well are described. The specific changes of the membrane potential and the cellular ion homoeostasis in adrenal cells expressing the different mutants are compared, and their impact on autonomous aldosterone production and proliferation is discussed.
authors.affiliation: Medical Cell Biology, University of Regensburg, Regensburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Bandulik
mesh_terms: D000450:Aldosterone / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000378:metabolism; D020747:Calcium Channels, T-Type / Q000235:genetics / Q000378:metabolism; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000235:genetics / Q000378:metabolism; D000073659:Gain of Function Mutation; D006801:Humans; D006929:Hyperaldosteronism / Q000209:etiology*; D007473:Ion Channels / Q000235:genetics*; D016623:Ion Pumps / Q000235:genetics*; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: C472073:CACNA1D protein, human; C479952:CACNA1H protein, human; C495270:CTNNB1 protein, human; D020746:Calcium Channels, L-Type; D020747:Calcium Channels, T-Type; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D007473:Ion Channels; D016623:Ion Pumps; C484274:KCNJ5 protein, human; D051176:beta Catenin; D000450:Aldosterone; C499076:ATP1A1 protein, human; D053499:Plasma Membrane Calcium-Transporting ATPases; C506962:ATP2B3 protein, human; D000254:Sodium-Potassium-Exchanging ATPase
keywords: aldosterone-producing adenoma; calcium signalling; glomerulosa cell; membrane potential; primary aldosteronism