Dual Role of CACNA1C/CaV1.2 in Cardiac and Neuropsychiatric Disease
9 affiliations
- 1Institute of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Marburg University, Karl-von-Frisch-Str. 2 K|03, 35043 Marburg, Germany
- 2Social and Affective Neuroscience Research Group, Laboratory of Biological Psychology, Research Unit Brain and Cognition, Faculty of Psychology and Educational Sciences, KU Leuven, 3000 Leuven, Belgium
- 3Leuven Brain Institute, KU Leuven, 3000 Leuven, Belgium
- 4A.I.Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70211 Kuopio, Finland
- 5Institute for Biomedicine, Eurac Research, 39100 Bolzano, Italy
- 6Department of Psychiatry, University of Münster, 48149 Münster, Germany
- 7Cells in Motion Interfaculty Cluster, University of Münster, 48149 Münster, Germany
- 8Social and Affective Neuroscience, Experimental and Biological Psychology, Faculty of Psychology, Marburg University, 35037 Marburg, Germany
- 9Center for Mind, Brain and Behavior (CMBB), Marburg University, 35032 Marburg, Germany
Abstract
The CACNA1C gene encodes the α1C subunit of voltage-gated CaV1.2 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/CaV1.2 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/CaV1.2 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/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.
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BibTeX
@article{konigstein2026dual,
title = {{Dual Role of CACNA1C/CaV1.2 in Cardiac and Neuropsychiatric Disease}},
author = {David Königstein and Theresa M. Kisko and Susanne Michels and Judith Alferink and Markus Wöhr and Carsten Culmsee and Jens Kockskämper},
journal = {Biomolecules},
year = {2026},
month = oct,
doi = {10.3390/biom16101459},
url = {https://www.mdpi.com/2218-273X/16/10/1459},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Dual Role of CACNA1C/CaV1.2 in Cardiac and Neuropsychiatric Disease
AU - David Königstein
AU - Theresa M. Kisko
AU - Susanne Michels
AU - Judith Alferink
AU - Markus Wöhr
AU - Carsten Culmsee
AU - Jens Kockskämper
PY - 2026
DA - 2026/10/01
JO - Biomolecules
DO - 10.3390/biom16101459
UR - https://www.mdpi.com/2218-273X/16/10/1459
AB - The CACNA1C gene encodes the α1C subunit of voltage-gated CaV1.2 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/CaV1.2 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/CaV1.2 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/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.
SN - 2218-273X
ER -