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原发性人肾上腺皮质细胞内钙离子动力学的新型研究方法。

Intracellular Calcium Dynamics in Primary Human Adrenocortical Cells Deciphered with a Novel Pipeline.

机构信息

Specialized Center of Excellence for Hypertension of the European Society of Hypertension and Emergency Medicine Unit, Department of Medicine-DIMED, University Hospital, University of Padua, Padua, 35126, Italy.

Neuroscience Institute, Italian National Research Council (CNR) and Department of Biomedical Sciences, University of Padua, Padua, 35131, Italy.

出版信息

High Blood Press Cardiovasc Prev. 2024 May;31(3):299-308. doi: 10.1007/s40292-024-00641-5. Epub 2024 May 20.

DOI:10.1007/s40292-024-00641-5
PMID:38763953
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11602809/
Abstract

INTRODUCTION

The fluctuations of the intracellular Ca concentration ([Ca]) are key physiological signals for cell function under normal conditions and can undergo profound alterations in disease states, as high blood pressure due to endocrine disorders like primary aldosteronism (PA). However, when assessing such fluctuations several parameters in the Ca signal dynamics need to be considered, which renders their assessment challenging.

AIM

Aim to develop an observer-independent custom-made pipeline to analyze Ca dynamics in terms of frequency and peak parameters, as amplitude, full width at half maximum (FWHM) and area under the curve (AUC).

METHODS

We applied a custom-made methodology to aldosterone-producing adenoma (APA) and APA adjacent cells (AAC) and found this pipeline to be suitable for monitoring and processing a wide-range of [Ca] events in these cell types delivering reproducible results.

CONCLUSION

The designed pipeline can provide a useful tool for [Ca] signal analysis that allows comparisons of Ca dynamics not only in PA, but in other cell phenotypes that are relevant for the regulation of blood pressure.

摘要

简介

细胞内钙离子浓度 ([Ca]) 的波动是细胞在正常情况下发挥功能的关键生理信号，在疾病状态下会发生深刻的改变，如内分泌紊乱引起的高血压，如原发性醛固酮增多症 (PA)。然而，在评估这种波动时，需要考虑钙信号动力学中的几个参数，这使得评估具有挑战性。

目的

旨在开发一种独立于观察者的定制流水线，以分析频率和峰值参数，如幅度、半峰全宽 (FWHM) 和曲线下面积 (AUC) 的钙动力学。

方法

我们应用了一种定制的方法来分析醛固酮分泌腺瘤 (APA) 和 APA 相邻细胞 (AAC)，并发现该流水线适用于监测和处理这些细胞类型中广泛的 [Ca] 事件，提供可重复的结果。

结论

设计的流水线可以为 [Ca] 信号分析提供有用的工具，不仅可以比较 PA 中的钙动力学，还可以比较与血压调节相关的其他细胞表型中的钙动力学。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6e1/11602809/980345ba6a0d/40292_2024_641_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6e1/11602809/f512d339b20e/40292_2024_641_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6e1/11602809/a806410e3937/40292_2024_641_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6e1/11602809/cc8a0b5ecc07/40292_2024_641_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6e1/11602809/efa1cc144a36/40292_2024_641_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6e1/11602809/5815ea8a7009/40292_2024_641_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6e1/11602809/980345ba6a0d/40292_2024_641_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6e1/11602809/f512d339b20e/40292_2024_641_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6e1/11602809/a806410e3937/40292_2024_641_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6e1/11602809/cc8a0b5ecc07/40292_2024_641_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6e1/11602809/efa1cc144a36/40292_2024_641_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6e1/11602809/5815ea8a7009/40292_2024_641_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6e1/11602809/980345ba6a0d/40292_2024_641_Fig6_HTML.jpg

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Somatic mutations of CADM1 in aldosterone-producing adenomas and gap junction-dependent regulation of aldosterone production.醛固酮瘤中 CADM1 的体细胞突变和缝隙连接依赖性的醛固酮产生调节。
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Intrinsic Adrenal TWIK-Related Acid-Sensitive TASK Channel Dysfunction Produces Spontaneous Calcium Oscillations Sufficient to Drive AngII (Angiotensin II)-Unresponsive Hyperaldosteronism.
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