Dual Role of CACNA1C/CaV1.2 in Cardiac and Neuropsychiatric Disease

27/10/2026

AI Summary

CACNA1C encodes CaV1.2 channels essential for cardiac and neuronal function; altered expression or function associates with cardiovascular and neuropsychiatric disorders.
Gain-of-function CACNA1C mutations cause Timothy syndrome; complete loss is lethal in mice, while haploinsufficiency models reveal behavioural and cellular abnormalities.
CACNA1C/CaV1.2 dysfunction links cardiac and neuropsychiatric disease; targeting it may treat both conditions with a single patient-selective drug.

TL;DR (AI Generated)

Clinical and genetic evidence implicates altered expression and/or function of CACNA1C/CaV1.2 in both cardiac and neuropsychiatric disease, including hypertension, cardiac arrhythmias, coronary artery disease, schizophrenia, bipolar disorder, depression, and autism.

The development of viable mouse and rat models with Cacna1c haploinsufficiency has allowed us to study the consequences of reduced expression and function of Cacna1c/CaV1.2 for heart and brain function from the molecular and cellular to the behavioral level.

Results lend further support to the notion that CACNA1C/CaV1.2 dysfunction represents a common link between cardiac and neuropsychiatric disorders and that appropriately targeting CACNA1C/CaV1.2 in selected patients may hold the promise of treating both conditions effectively with a single drug.

Basic summary

Biomolecules. 2026 Oct 7;16(10):1459. doi: 10.3390/biom16101459.

ABSTRACT

The CACNA1C gene encodes the α_1C subunit of voltage-gated Ca_V1.2 calcium channels, serving many pivotal functions throughout the body, including in the heart and brain. Clinical and genetic evidence implicates altered expression and/or function of CACNA1C/Ca_V1.2 in both cardiac and neuropsychiatric disease, including hypertension, cardiac arrhythmias, coronary artery disease, schizophrenia, bipolar disorder, depression, and autism. Gain-of-function mutations in CACNA1C cause Timothy syndrome, a potentially lethal multi-organ disorder with severe cardiac and neuropsychiatric defects. Conversely, the complete loss of Cacna1c is lethal in mice. The development of viable mouse and rat models with Cacna1c haploinsufficiency has allowed us to study the consequences of reduced expression and function of Cacna1c/Ca_V1.2 for heart and brain function from the molecular and cellular to the behavioral level. We review recent findings from these rodent models, revealing (i) alterations in behavior and (ii) in neuronal and non-neuronal function, as well as (iii) an impaired ability of the heart and its cardiomyocytes to adapt to (sympathetic) stress. Results lend further support to the notion that CACNA1C/Ca_V1.2 dysfunction represents a common link between cardiac and neuropsychiatric disorders and that appropriately targeting CACNA1C/Ca_V1.2 in selected patients may hold the promise of treating both conditions effectively with a single drug.