Key result
Slower-inactivating bacterial sodium channels beat endogenous currents in preventing conduction block and arrhythmias in silico.
Why the study?
Slow action potential conduction commonly causes cardiac arrhythmias, yet current pharmacotherapies cannot augment cardiac conduction.
Does expression of prokaryotic voltage-gated sodium channels (BacNav) improve cardiac action potential conduction compared to augmenting endogenous Nav1.5 channels in in silico models?
Does expression of prokaryotic voltage-gated sodium channels (BacNav) improve cardiac action potential conduction compared to augmenting endogenous Nav1.5 channels in in silico models?
In silico modeling demonstrates that gene therapy using slower-inactivating bacterial sodium channels (BacNav) may provide greater antiarrhythmic benefits than enhancing endogenous Nav1.5 current in hearts with compromised conduction.
Does not support clinical use; leaves open whether BacNav superiority extends beyond in silico models.
Slow action potential conduction is a common cause of various cardiac arrhythmias; yet, current pharmacotherapies cannot augment cardiac conduction. This in silico study compared the efficacy of recently proposed antiarrhythmic gene therapy approaches that increase peak sodium current in cardiomyocytes. When compared with the augmentation of endogenous sodium current, expression of slower-inactivating bacterial sodium channels was superior in preventing conduction block and arrhythmia induction. These results further the promise of antiarrhythmic gene therapies targeting sodium channels.
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Needs et al. (2023) studied Cardiac arrhythmias. Expression of slower-inactivating bacterial sodium channels vs. Augmentation of endogenous sodium current was evaluated on Prevention of conduction block and arrhythmia induction. Expression of slower-inactivating bacterial sodium channels was superior to augmenting endogenous sodium current in preventing conduction block and arrhythmia induction in an in silico model.
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