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CACNA1C-Related Channelopathies

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Voltage-gated Ca2+ Channels: Pharmacology, Modulation and their Role in Human Disease

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 279))

Abstract

The CACNA1C gene encodes the pore-forming subunit of the CaV1.2 L-type Ca2+ channel, a critical component of membrane physiology in multiple tissues, including the heart, brain, and immune system. As such, mutations altering the function of these channels have the potential to impact a wide array of cellular functions. The first mutations identified within CACNA1C were shown to cause a severe, multisystem disorder known as Timothy syndrome (TS), which is characterized by neurodevelopmental deficits, long-QT syndrome, life-threatening cardiac arrhythmias, craniofacial abnormalities, and immune deficits. Since this initial description, the number and variety of disease-associated mutations identified in CACNA1C have grown tremendously, expanding the range of phenotypes observed in affected patients. CACNA1C channelopathies are now known to encompass multisystem phenotypes as described in TS, as well as more selective phenotypes where patients may exhibit predominantly cardiac or neurological symptoms. Here, we review the impact of genetic mutations on CaV1.2 function and the resultant physiological consequences.

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Author notes

  1. Kevin G. Herold and John W. Hussey contributed equally to this work.

Authors and Affiliations

  1. Department of Physiology, University of Maryland School of Medicine, Baltimore, MD, USA

    Kevin G. Herold, John W. Hussey & Ivy E. Dick

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  1. Kevin G. Herold
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  2. John W. Hussey
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  3. Ivy E. Dick
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Correspondence to Ivy E. Dick .

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  1. Center for Chemistry and Biomedicine, UI, Pharmacology and Toxicology, Innsbruck, Austria

    Jörg Striessnig

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Herold, K.G., Hussey, J.W., Dick, I.E. (2023). CACNA1C-Related Channelopathies. In: Striessnig, J. (eds) Voltage-gated Ca2+ Channels: Pharmacology, Modulation and their Role in Human Disease. Handbook of Experimental Pharmacology, vol 279. Springer, Cham. https://doi.org/10.1007/164_2022_624

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