Evidence mapPaperPMID 36129175Full record

ArticleHypertension (Dallas, Tex. : 1979)2022

Intrinsic Adrenal TWIK-Related Acid-Sensitive TASK Channel Dysfunction Produces Spontaneous Calcium Oscillations Sufficient to Drive AngII (Angiotensin II)-Unresponsive Hyperaldosteronism.

Christina A Gancayco, Molly R Gerding, David T Breault, Mark P Beenhakker, Paula Q Barrett, Nick A Guagliardo

Open access · bronzeAbstract read
In one paragraph

Article in Hypertension (Dallas, Tex. : 1979), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.3field-weighted citation impact, top 19% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 10 citations in OpenAlex.

  1. Article
  2. Article
  3. Intracellular Calcium Dynamics in Primary Human Adrenocortical Cells Deciphered with a Novel Pipeline.High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension · 2024
    Article
  4. Article
  5. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Christina A GancaycoMedicine-Research Computing (C.A.G.), University of Virginia, Charlottesville.
Molly R GerdingDepartment of Pharmacology (M.R.G., M.P.B., P.Q.B., N.A.G.), University of Virginia, Charlottesville.
David T BreaultDivision of Endocrinology, Boston Children's Hospital, MA (D.T.B.).
Mark P BeenhakkerDepartment of Pharmacology (M.R.G., M.P.B., P.Q.B., N.A.G.), University of Virginia, Charlottesville.
Paula Q BarrettDepartment of Pharmacology (M.R.G., M.P.B., P.Q.B., N.A.G.), University of Virginia, Charlottesville.ORCID 0000-0003-2052-3899
Nick A GuagliardoDepartment of Pharmacology (M.R.G., M.P.B., P.Q.B., N.A.G.), University of Virginia, Charlottesville.ORCID 0000-0003-2539-1346
University of Virginia · USBoston Children's Hospital · US

Funding

Rosettes in Adrenal Development, Maintenance and DiseaseR01DK123694 · BOSTON CHILDREN'S HOSPITAL · 2025 to 2025
$756k
NHLBI NIH HHS R01 HL089717NHLBI NIH HHS R01 HL138241NIDDK NIH HHS R01 DK123694
6 · The paper itself

Abstract

backgroundIon channel mutations in calcium regulating genes strongly associate with AngII (angiotensin II)-independent aldosterone production. Here, we used an established mouse model of in vivo aldosterone autonomy,

methodsWe imaged calcium activity in adrenal slices expressing a zG-specific calcium reporter (GCaMP3), an in vitro experimental approach that preserves the native rosette assembly and removes potentially confounding extra-adrenal contributions. In parallel experiments, we measured acute aldosterone production from adrenal slice cultures.

resultsAbsent from untreated WT slices, we find that either adrenal-specific genetic deletion or acute pharmacological TASK channel inhibition produces spontaneous oscillatory bursting behavior and steroidogenic activity (2.4-fold) that are robust, sustained, and equivalent to activities evoked by 3 nM AngII in WT slices. Moreover, spontaneous activity in zG-TASK-loss-of-function slices and inhibitor-evoked activity in WT slices are unresponsive to AngII regulation over a wide range of concentrations (50 pM to 3 µM).

conclusionsWe provide proof of principle that spontaneous activity of zG cells within classic rosette assemblies evoked solely by a change in an intrinsic, dominant resting-state conductance can be a significant source of AngII-independent aldosterone production from native tissue.

Indexed as

AldosteroneHyperaldosteronismAngiotensin IIAnimalsCalciumCalcium SignalingMiceZona GlomerulosaAldosteroneAngiotensin IICalciumaldosteroneprimary hyperaldosteronismrenin-angiotensin systemTWIK-related acid-sensitive potassium channelzona glomerulosa

Identifiers

PMID36129175
PMCPMC10167771
OpenAlexW4297874955

What Socratic holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.