Asset Details
Do you wish to reserve the book?
Na V 1.8 as Proarrhythmic Target in a Ventricular Cardiac Stem Cell Model
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Na V 1.8 as Proarrhythmic Target in a Ventricular Cardiac Stem Cell Model
Do you wish to request the book?
Na V 1.8 as Proarrhythmic Target in a Ventricular Cardiac Stem Cell Model
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Na V 1.8 as Proarrhythmic Target in a Ventricular Cardiac Stem Cell Model
2024
Overview
The sodium channel Na
1.8, encoded by the
gene, has recently emerged as a potential regulator of cardiac electrophysiology. We have previously shown that Na
1.8 contributes to arrhythmogenesis by inducing a persistent Na
current (late Na
current, I
) in human atrial and ventricular cardiomyocytes (CM). We now aim to further investigate the contribution of Na
1.8 to human ventricular arrhythmogenesis at the CM-specific level using pharmacological inhibition as well as a genetic knockout (KO) of
in induced pluripotent stem cell CM (iPSC-CM). In functional voltage-clamp experiments, we demonstrate that I
was significantly reduced in ventricular
-KO iPSC-CM and in control CM after a specific pharmacological inhibition of Na
1.8. In contrast, we did not find any effects on ventricular APD
. The frequency of spontaneous sarcoplasmic reticulum Ca
sparks and waves were reduced in
KO iPSC-CM and control cells following the pharmacological inhibition of Na
1.8. We further analyzed potential triggers of arrhythmias and found reduced delayed afterdepolarizations (DAD) in
KO iPSC-CM and after the specific inhibition of Na
1.8 in control cells. In conclusion, we show that Na
1.8-induced I
primarily impacts arrhythmogenesis at a subcellular level, with minimal effects on systolic cellular Ca
release. The inhibition or knockout of Na
1.8 diminishes proarrhythmic triggers in ventricular CM. In conjunction with our previously published results, this work confirms Na
1.8 as a proarrhythmic target that may be useful in an anti-arrhythmic therapeutic strategy.
Subject
Action Potentials - drug effects
/ Arrhythmias, Cardiac - etiology
/ Arrhythmias, Cardiac - genetics
/ Arrhythmias, Cardiac - metabolism
/ Heart Ventricles - metabolism
/ Humans
/ Induced Pluripotent Stem Cells - cytology
/ Induced Pluripotent Stem Cells - metabolism
/ Myocytes, Cardiac - drug effects
/ Myocytes, Cardiac - metabolism
