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

• Applicant: Dr. Gabriel Stölting
• Subject Area: Anatomy and Physiology
• Term: from 2018 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 413724788

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.

• DFG Programme: Research Grants