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Updated: May 8, 2026
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Determination of the Relative Cell Surface and Total Expression of Recombinant Ion Channels Using Flow Cytometry
Published on: September 28, 2016
Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism
Igor Splawski1, Katherine W Timothy, Leah M Sharpe
1Department of Cardiology, Children's Hospital, Harvard Medical School and Howard Hughes Medical Institute, Boston, MA 02115, USA. igor@enders.tch.harvard.edu
Cell
|September 30, 2004
Summary
Timothy syndrome, a disorder affecting multiple organs, is caused by a specific mutation in the Ca(V)1.2 calcium channel. This mutation leads to dangerous heart arrhythmias and developmental issues, including autism.
Area of Science:
- Cardiovascular Physiology
- Developmental Biology
- Genetics
Background:
- The Ca(V)1.2 calcium channel is crucial for cardiac function, but its role in other organs and developmental processes is not fully understood.
- Understanding the precise molecular mechanisms underlying calcium channelopathies is essential for diagnosing and treating related disorders.
Observation:
- Timothy syndrome is a newly identified disorder presenting with severe multiorgan dysfunction, including lethal arrhythmias, congenital heart defects, immune deficiency, and cognitive abnormalities.
- All identified cases of Timothy syndrome share a single, de novo missense mutation (G406R) in the Ca(V)1.2 gene, which is expressed across all affected tissues.
Findings:
- The G406R mutation in Ca(V)1.2 disrupts channel inactivation, leading to sustained inward calcium currents and potential intracellular calcium overload in various cell types.
- In cardiomyocytes, this prolonged calcium influx delays repolarization, significantly increasing the risk of fatal cardiac arrhythmias.
Implications:
- This research highlights the critical role of Ca(V)1.2 in overall human physiology and development, extending beyond its known cardiac functions.
- The findings suggest that dysregulated calcium signaling, mediated by Ca(V)1.2, may be implicated in the pathogenesis of autism spectrum disorder.
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