Key result
Deletion or pharmacological inhibition of the TRPV4 channel in mice shortened the QT interval and reduced the action potential duration of ventricular myocytes.
Why the study?
Does TRPV4 channel modulation affect ventricular electrical activity in mouse models?
Does TRPV4 channel modulation affect ventricular electrical activity in mouse models?
This study provides the first evidence that the TRPV4 channel participates in ventricular electrical activity by carrying an inward current that slows action potential repolarization.
No immediate clinical implications from mouse data; leaves open TRPV4 as a target for modulating human ventricular repolarization.
Transient receptor potential vanilloid 4 (TRPV4) is expressed at the membrane of mouse ventricular myocytes and colocalizes with non-T-tubular L-type calcium channels. Deletion of trpv4 gene in mice results in shortened QT interval on electrocardiogram and reduced action potential duration of ventricular myocytes. Pharmacological activation of TRPV4 channel leads to increased action potential duration and increased calcium transient amplitude in trpv4 −/− but not in trpv4 −/− ventricular myocytes. To the contrary, TRPV4 channel pharmacological inhibition reduces action potential duration in trpv4 +/+ but not in trpv4 −/− myocytes. Integration of TRPV4 channel in a computational model of mouse action potential shows that the channel carries an inward current contributing to slowing down action potential repolarization and to increase calcium transient amplitude, similarly to what is observed experimentally. This study highlights for the first time the involvement of TRPV4 channel in ventricular electrical activity.
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Chaigne et al. (2021) studied Ventricular electrical activity. trpv4 gene deletion and pharmacological modulation vs. trpv4 +/+ (wild type) mice was evaluated on QT interval and action potential duration. Deletion or pharmacological inhibition of the TRPV4 channel in mice shortened the QT interval and reduced the action potential duration of ventricular myocytes.
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