CaV3.2 (CACNA1H) in Primary Aldosteronism

doi:10.1007/164_2023_660

Review

. 2023:279:249-262.

doi: 10.1007/164_2023_660.

Ca_V3.2 (CACNA1H) in Primary Aldosteronism

Hoang An Dinh^#¹, Gabriel Stölting^#¹, Ute I Scholl^{2

3}

Affiliations

¹ Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Center of Functional Genomics, Berlin, Germany.
² Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Center of Functional Genomics, Berlin, Germany. ute.scholl@bih-charite.de.
³ Department of Nephrology and Medical Intensive Care, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany. ute.scholl@bih-charite.de.

^# Contributed equally.

PMID: 37311830
DOI: 10.1007/164_2023_660

Review

Ca_V3.2 (CACNA1H) in Primary Aldosteronism

Hoang An Dinh et al. Handb Exp Pharmacol. 2023.

. 2023:279:249-262.

doi: 10.1007/164_2023_660.

Authors

Hoang An Dinh^#¹, Gabriel Stölting^#¹, Ute I Scholl^{2

3}

Affiliations

¹ Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Center of Functional Genomics, Berlin, Germany.
² Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Center of Functional Genomics, Berlin, Germany. ute.scholl@bih-charite.de.
³ Department of Nephrology and Medical Intensive Care, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany. ute.scholl@bih-charite.de.

^# Contributed equally.

PMID: 37311830
DOI: 10.1007/164_2023_660

Abstract

Aldosterone is a steroid hormone produced in the zona glomerulosa (ZG) of the adrenal cortex. The most prominent function of aldosterone is the control of electrolyte homeostasis and blood pressure via the kidneys. The primary factors regulating aldosterone synthesis are the serum concentrations of angiotensin II and potassium. The T-type voltage-gated calcium channel Ca_V3.2 (encoded by CACNA1H) is an important component of electrical as well as intracellular calcium oscillations, which govern aldosterone production in the ZG. Excessive aldosterone production that is (partially) uncoupled from physiological stimuli leads to primary aldosteronism, the most common cause of secondary hypertension. Germline gain-of-function mutations in CACNA1H were identified in familial hyperaldosteronism, whereas somatic mutations are a rare cause of aldosterone-producing adenomas. In this review, we summarize these findings, put them in perspective, and highlight missing knowledge.

Keywords: Aldosterone; CACNA1H; CaV3.2; Calcium channel; Primary aldosteronism.

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Cited by

A Review of the CACNA Gene Family: Its Role in Neurological Disorders.
Szymanowicz O, Drużdż A, Słowikowski B, Pawlak S, Potocka E, Goutor U, Konieczny M, Ciastoń M, Lewandowska A, Jagodziński PP, Kozubski W, Dorszewska J. Szymanowicz O, et al. Diseases. 2024 May 5;12(5):90. doi: 10.3390/diseases12050090. Diseases. 2024. PMID: 38785745 Free PMC article. Review.

References

1. Akizuki O, Inayoshi A, Kitayama T et al (2008) Blockade of T-type voltage-dependent Ca2+ channels by benidipine, a dihydropyridine calcium channel blocker, inhibits aldosterone production in human adrenocortical cell line NCI-H295R. Eur J Pharmacol 584:424–434. https://doi.org/10.1016/j.ejphar.2008.02.001 - DOI - PubMed
1. Azizan EAB, Poulsen H, Tuluc P et al (2013) Somatic mutations in ATP1A1 and CACNA1D underlie a common subtype of adrenal hypertension. Nat Genet 45:1055–1060. https://doi.org/10.1038/ng.2716 - DOI - PubMed
1. Beuschlein F, Boulkroun S, Osswald A et al (2013) Somatic mutations in ATP1A1 and ATP2B3 lead to aldosterone-producing adenomas and secondary hypertension. Nat Genet 45:440–444. 444e1-2 - DOI - PubMed
1. Blesneac I, Chemin J, Bidaud I et al (2015) Phosphorylation of the Cav3.2 T-type calcium channel directly regulates its gating properties. Proc Natl Acad Sci U S A 112:13705–13710 - DOI - PubMed - PMC
1. Carbone E, Lux HD (1984) A low voltage-activated, fully inactivating ca channel in vertebrate sensory neurones. Nature 310:501–502. https://doi.org/10.1038/310501a0 - DOI - PubMed

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[1] Akizuki O, Inayoshi A, Kitayama T et al (2008) Blockade of T-type voltage-dependent Ca2+ channels by benidipine, a dihydropyridine calcium channel blocker, inhibits aldosterone production in human adrenocortical cell line NCI-H295R. Eur J Pharmacol 584:424–434. https://doi.org/10.1016/j.ejphar.2008.02.001 - DOI - PubMed

[2] Akizuki O, Inayoshi A, Kitayama T et al (2008) Blockade of T-type voltage-dependent Ca2+ channels by benidipine, a dihydropyridine calcium channel blocker, inhibits aldosterone production in human adrenocortical cell line NCI-H295R. Eur J Pharmacol 584:424–434. https://doi.org/10.1016/j.ejphar.2008.02.001 - DOI - PubMed

[3] Azizan EAB, Poulsen H, Tuluc P et al (2013) Somatic mutations in ATP1A1 and CACNA1D underlie a common subtype of adrenal hypertension. Nat Genet 45:1055–1060. https://doi.org/10.1038/ng.2716 - DOI - PubMed

[4] Azizan EAB, Poulsen H, Tuluc P et al (2013) Somatic mutations in ATP1A1 and CACNA1D underlie a common subtype of adrenal hypertension. Nat Genet 45:1055–1060. https://doi.org/10.1038/ng.2716 - DOI - PubMed

[5] Beuschlein F, Boulkroun S, Osswald A et al (2013) Somatic mutations in ATP1A1 and ATP2B3 lead to aldosterone-producing adenomas and secondary hypertension. Nat Genet 45:440–444. 444e1-2 - DOI - PubMed

[6] Beuschlein F, Boulkroun S, Osswald A et al (2013) Somatic mutations in ATP1A1 and ATP2B3 lead to aldosterone-producing adenomas and secondary hypertension. Nat Genet 45:440–444. 444e1-2 - DOI - PubMed

[7] Blesneac I, Chemin J, Bidaud I et al (2015) Phosphorylation of the Cav3.2 T-type calcium channel directly regulates its gating properties. Proc Natl Acad Sci U S A 112:13705–13710 - DOI - PubMed - PMC

[8] Blesneac I, Chemin J, Bidaud I et al (2015) Phosphorylation of the Cav3.2 T-type calcium channel directly regulates its gating properties. Proc Natl Acad Sci U S A 112:13705–13710 - DOI - PubMed - PMC

[9] Carbone E, Lux HD (1984) A low voltage-activated, fully inactivating ca channel in vertebrate sensory neurones. Nature 310:501–502. https://doi.org/10.1038/310501a0 - DOI - PubMed

[10] Carbone E, Lux HD (1984) A low voltage-activated, fully inactivating ca channel in vertebrate sensory neurones. Nature 310:501–502. https://doi.org/10.1038/310501a0 - DOI - PubMed

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Ca_V3.2 (CACNA1H) in Primary Aldosteronism

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