The Role of Chloride and Calcium Channels for Calcium Signalling in the Zona glomerulosa

肾上腺的最外层，即肾小球带，负责矿物皮质激素醛固酮的产生。由于醛固酮是高度亲脂性的，它的血清浓度必须在合成水平上进行调节。醛固酮在靶器官如肾脏中，通过与细胞内受体结合，控制多种基因的表达，增加氯化钠和水的重吸收，同时排出钾，导致动脉血压升高。大约6%的动脉高血压病例是由醛固酮不受控制的病理性合成引起的原发性高醛固酮增多症的结果。最近的研究表明，编码离子通道和转运体的基因改变——无论是醛固酮产生性腺瘤的体细胞突变，还是家族性高醛固酮增多症的种系突变——都是许多原发性醛固酮增多症的潜在原因。基于我们最近在这一领域的贡献，我们将研究钙离子和氯离子在肾小球带细胞电兴奋性中的作用，特别是钙通道CaV1.3和CaV3.2以及氯通道ClC-2的作用。为此，我们建立了急性肾上腺片制剂，利用钙显像和膜片钳电生理以及其他支持方法来研究肾小球带的功能。我们对许多相关离子通道的敲除和敲入小鼠模型的访问将使我们能够在细胞水平上揭示它们对肾小球带生理学和病理生理学的贡献。

The outermost layer of the adrenal gland, the zona glomerulosa, is tasked with the production of the mineralocorticoid aldosterone. As aldosterone is highly lipophilic, its serum concentration must be regulated on the level of synthesis. In its target organs, e.g. the kidney, aldosterone associates with intracellular receptors and controls the expression of diverse genes to increase sodium chloride and water reabsorption while excreting potassium resulting in an increase of the arterial blood pressure. About 6% of all cases of arterial hypertension are the result of primary hyperaldosteronism caused by an unregulated, pathological synthesis of aldosterone. Recent studies suggest that changes to genes encoding ion channels and transporters—either as somatic mutations in aldosterone-producing adenomas or germline mutations in familial hyperaldosteronism—are underlying many cases of primary aldosteronism. Based on our recent contributions to this field, we will study the role of calcium and chloride ions in the electrical excitability of zona glomerulosa cells in general and the role of the calcium channels CaV1.3 and CaV3.2 as well as the chloride channel ClC-2 in particular. To this end, we established acute adrenal gland slice preparations to investigate zona glomerulosa function using calcium imaging and patch clamp electrophysiology as well as further supporting methods. Our access to knock-out and knock-in mouse models of many involved ion channels will allow us to unravel their contributions to zona glomerulosa physiology and pathophysiology on a cellular level.