1. Task3 Potassium Channel Gene Invalidation Causes Low Renin and Salt-Sensitive Arterial Hypertension
- Author
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Markus Reichold, Maria-Christina Zennaro, Philipp Tauber, Florian Lesage, Thomas Budde, Sophia Haubs, Lu Dang Cong, Abeer El Wakil, Sascha Bandulik, Jacques Barhanin, Enzo Lalli, Richard Warth, Frank Schweda, David Penton, Medical Cell Biology, Universität Regensburg (UR), Institute of Physiology, Laboratoire de PhysioMédecine Moléculaire (LP2M), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Institut de pharmacologie moléculaire et cellulaire (IPMC), Department of Biological Sciences ((A.E.W.)), Université d'Alexandrie, Institut für Physiologie I, Westfälische Wilhelms-Universität Münster (WWU), Ion Channel Science and Therapeutics, Laboratories of Excellence, Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Université Paris Descartes - Paris 5 (UPD5)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Université Côte d'Azur (UCA), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), University of Regensburg, University Regensburg, Laboratoire de PhysioMédecine Moléculaire ( LP2M ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de pharmacologie moléculaire et cellulaire ( IPMC ), Department of Biological Sciences ( (A.E.W.) ), Westfälische Wilhelms-Universität, Paris-Centre de Recherche Cardiovasculaire ( PARCC - U970 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Université Paris Descartes - Paris 5 ( UPD5 ), and Université Côte d'Azur ( UCA )
- Subjects
medicine.medical_specialty ,Potassium Channels ,Sodium ,chemistry.chemical_element ,030209 endocrinology & metabolism ,Blood Pressure ,Biology ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Endocrinology ,Internal medicine ,[ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology ,Renin–angiotensin system ,Adrenal Glands ,Renin ,medicine ,Animals ,Secretion ,Sodium Chloride, Dietary ,Aldosterone ,Cells, Cultured ,030304 developmental biology ,Calcium metabolism ,Membrane potential ,Mice, Knockout ,0303 health sciences ,Adaptation, Physiological ,Potassium channel ,Blood pressure ,Phenotype ,chemistry ,Hypertension ,Calcium ,Zona Glomerulosa ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
Task1 and Task3 potassium channels (Task: tandem of P domains in a weak inward rectifying K+ channel-related acid-sensitive K+ channel) are believed to control the membrane voltage of aldosterone-producing adrenal glomerulosa cells. This study aimed at understanding the role of Task3 for the control of aldosterone secretion. The adrenal phenotype of Task3−/− mice was investigated using electrophysiology, adrenal slices, and blood pressure measurements. Primary adrenocortical cells of Task3−/− mice were strongly depolarized compared with wild-type (−52 vs. −79 mV), and in fresh adrenal slices Ca2+ signaling of Task3−/− glomerulosa cells was abnormal. In living Task3−/− mice, the regulation of aldosterone secretion showed specific deficits: Under low Na+ and high K+ diets, protocols known to increase aldosterone, and under standard diet, Task3 inactivation was compensated and aldosterone was normal. However, high Na+ and low K+ diets, two protocols known to lower aldosterone, failed to lower aldosterone in Task3−/− mice. The physiological regulation of aldosterone was disturbed: aldosterone-renin ratio, an indicator of autonomous aldosterone secretion, was 3-fold elevated at standard and high Na+ diets. Isolated adrenal glands of Task3−/− produced 2-fold more aldosterone. As a consequence, Task3−/− mice showed salt-sensitive arterial hypertension (plus 10 mm Hg). In conclusion, Task3 plays an important role in the adaptation of aldosterone secretion to dietary salt intake.
- Published
- 2012
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