T- and L-Type Calcium Channels Maintain Calcium Oscillations in the Murine Zona Glomerulosa.

Autor: Dinh HA; Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Center of Functional Genomics, Germany (H.A.D., M.V., A.K.S., U.I.S., G.S.).; Charité - Universitätsmedizin Berlin, Department of Translational Physiology, Germany (H.A.D.)., Volkert M; Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Center of Functional Genomics, Germany (H.A.D., M.V., A.K.S., U.I.S., G.S.)., Secener AK; Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Center of Functional Genomics, Germany (H.A.D., M.V., A.K.S., U.I.S., G.S.).; Genomics Technology Platform, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany (A.K.S.).; Institute of Chemistry and Biochemistry, Department of Biology, Chemistry and Pharmacy, Freie Universität Berlin, Germany (A.K.S.)., Scholl UI; Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Center of Functional Genomics, Germany (H.A.D., M.V., A.K.S., U.I.S., G.S.).; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Nephrology and Medical Intensive Care, Berlin, Germany (U.I.S.)., Stölting G; Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Center of Functional Genomics, Germany (H.A.D., M.V., A.K.S., U.I.S., G.S.).
Jazyk: angličtina
Zdroj: Hypertension (Dallas, Tex. : 1979) [Hypertension] 2024 Apr; Vol. 81 (4), pp. 811-822. Date of Electronic Publication: 2024 Feb 16.
DOI: 10.1161/HYPERTENSIONAHA.123.21798
Abstrakt: Background: The zona glomerulosa of the adrenal gland is responsible for the synthesis and release of the mineralocorticoid aldosterone. This steroid hormone regulates salt reabsorption in the kidney and blood pressure. The most important stimuli of aldosterone synthesis are the serum concentrations of angiotensin II and potassium. In response to these stimuli, voltage and intracellular calcium levels in the zona glomerulosa oscillate, providing the signal for aldosterone synthesis. It was proposed that the voltage-gated T-type calcium channel Ca V 3.2 is necessary for the generation of these oscillations. However, Cacna1h knock-out mice have normal plasma aldosterone levels, suggesting additional calcium entry pathways.
Methods: We used a combination of calcium imaging, patch clamp, and RNA sequencing to investigate calcium influx pathways in the murine zona glomerulosa.
Results: Cacna1h -/- glomerulosa cells still showed calcium oscillations with similar concentrations as wild-type mice. No calcium channels or transporters were upregulated to compensate for the loss of Ca V 3.2. The calcium oscillations observed were instead dependent on L-type voltage-gated calcium channels. Furthermore, we found that L-type channels can also partially compensate for an acute inhibition of Ca V 3.2 in wild-type mice. Only inhibition of both T- and L-type calcium channels abolished the increase of intracellular calcium caused by angiotensin II in wild-type.
Conclusions: Our study demonstrates that T-type calcium channels are not strictly required to maintain glomerulosa calcium oscillations and aldosterone production. Pharmacological inhibition of T-type channels alone will likely not significantly impact aldosterone production in the long term.
Competing Interests: None.
Databáze: MEDLINE
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