Key result
Mutation of the tmem161b gene in zebrafish and knockout in mice causes cardiac arrhythmias and prolonged action potential repolarization by increasing Ca2+ and K+ currents.
Why the study?
Does mutation of the tmem161b gene alter cardiac rhythm and action potential repolarization in preclinical models?
Does mutation of the tmem161b gene alter cardiac rhythm and action potential repolarization in preclinical models?
Tmem161b is identified as a novel, evolutionarily conserved regulator of cardiac rhythm that functions by inhibiting Ca2+ and K+ currents.
Answers are grounded in this paper and cite their sources.
Does not alter clinical practice; leaves open tmem161b's role in human arrhythmias.
Significance The heart initiates rhythmic contractions early during development. A unique zebrafish mutant with specific cardiac arrhythmia phenotypes was identified and mutation of the uncharacterized tmem161b gene shown to be causative. Tmem161b knockout mice are perinatal lethal and isolated embryonic cardiomyocytes exhibit arrhythmic Ca 2+ oscillations, suggesting functional conservation. Protein localization studies show Tmem161b is expressed in excitable cells and at cardiomyocyte plasma membranes. Imaging of in vivo action potentials shows tmem161b mutants have prolonged action potential repolarization. Patch-clamping of isolated cardiomyocytes confirms prolonged action potential repolarization and shows increased Ca 2+ and K + currents are likely the cause of altered action potential morphology. This suggests Tmem161b is a new conserved regulator of cardiac rhythm by inhibiting Ca 2+ and K + currents.
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Koopman et al. (2021) studied Cardiac arrhythmia. tmem161b mutation/knockout vs. Wild-type was evaluated on Cardiac rhythm and action potential repolarization. Mutation of the tmem161b gene in zebrafish and knockout in mice causes cardiac arrhythmias and prolonged action potential repolarization by increasing Ca2+ and K+ currents.
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