Researchers at The Ohio State University have made significant strides in understanding the cause of specific cardiac arrhythmia disorders, with their study spotlighting a protein called calmodulin.
Calmodulin’s crucial role in heart function involves regulating the movement of charged sodium and calcium molecules within heart-muscle cells.
This exchange orchestrates the rhythmic heartbeat and generates the electrical activity detected during an electrocardiogram.
Calmodulinopathies: A Fatal Heart Rhythm Disorder
Recently, research has unveiled that mutations in calmodulin can trigger severe heart rhythm disorders, collectively known as calmodulinopathies.
These often lethal conditions currently lack effective treatments, predominantly due to a limited understanding of how calmodulin mutations induce arrhythmias.
New Findings: Linking a Mutated Form of Calmodulin to Arrhythmias
Ohio State researchers from the colleges of Pharmacy, Medicine, and Engineering used an animal model to demonstrate how a mutated form of calmodulin, D96V-CaM, contributes to arrhythmias.
This mutated protein allows sodium ions to flow through molecular channels in heart-muscle cells, resulting in abnormal calcium ion release.
The researchers published their enlightening findings in the Journal of Clinical Investigation.
Towards New Therapies: Existing Drugs for an Incurable Disorder
The study uncovered a hitherto unknown dysregulation of sodium channels mediated by calmodulin, leading to calmodulinopathy. Principal investigator Przemysław Radwanski noted,
“Our findings may lead to the development of new therapies that are based on existing drugs to treat a severe congenital heart disorder that today is incurable.”
Testing a Therapeutic Approach: Targeting Affected Sodium Channels
Radwanski and his team used a genetically engineered mouse model to investigate whether focusing on the impacted sodium channels might offer a calmodulinopathy treatment. Key findings included:
- The mutated calmodulin D96V-CaM hinders a specific sodium channel known as NaV1.6;
- D96V-CaM does not impact the most common sodium channel in heart muscle, NaV1.5;
- D96V-CaM induces cardiac arrhythmias by causing the abnormal release of calcium ions.
A Step Forward: Preventing Arrhythmias from Calmodulin Mutations and Abnormal Sodium-Channel Function
“By understanding calmodulin-related heart diseases, we aim to discover approaches that will prevent arrhythmias that stem not only from calmodulin mutations but also from abnormal sodium-channel function, as seen in patients with congenital and acquired arrhythmia syndromes,” Radwanski said, underlining the study’s far-reaching implications.
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The study was published in the Journal of Clinical Investigation.
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