New experimental evidence for mechanism of arrhythmogenic membrane potential alternans based on balance of electrogenic I(NCX)/I(Ca) currents

Heart Rhythm : the Official Journal of the Heart Rhythm Society
Xiaoping WanDavid S Rosenbaum

Abstract

Computer simulations have predicted that the balance of various electrogenic sarcolemmal ion currents may control the amplitude and phase of beat-to-beat alternans of membrane potential (V(m)). However, experimental evidence for the mechanism by which alternans of calcium transients produces alternation of V(m) (V(m)-ALT) is lacking. To provide experimental evidence that Ca-to-V(m) coupling during alternans is determined by the balanced influence of 2 Ca-sensitive electrogenic sarcolemmal ionic currents: I(NCX) and I(Ca). V(m)-ALT and Ca-ALT were measured simultaneously from isolated guinea pig myocytes (n = 41) by using perforated patch and Indo-1(AM) fluorescence, respectively. There were 3 study groups: (1) control, (2) I(NCX) predominance created by adenoviral-induced NCX overexpression, and (3) I(Ca) predominance created by I(NCX) inhibition (SEA-0400) or enhanced I(Ca) (As(2)O(3)). During alternans, 14 of 14 control myocytes demonstrated positive Ca-to-V(m) coupling, consistent with I(NCX), but not I(Ca), as the major electrogenic current in modulating action potential duration. Positive Ca-to-V(m) coupling was maintained during I(NCX) predominance in 8 of 8 experiments with concurrent increase in Ca-to-V(m) gain (P <.05)...Continue Reading

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Citations

Oct 1, 2014·Physics Reports·Zhilin QuJames N Weiss
May 24, 2014·Biophysical Journal·Willemijn GroenendaalDavid J Christini
Dec 17, 2014·PLoS Computational Biology·Kelly C ChangNatalia A Trayanova
Jun 30, 2016·Channels·Giedrius Kanaporis, Lothar A Blatter
Oct 21, 2016·Scientific Reports·Zhilin QuMichael Nivala
Jan 11, 2017·Computational and Mathematical Methods in Medicine·Jiaqi LiuXiaopeng Zhao
Jul 2, 2017·Medicina·Giedrius Kanaporis, Lothar A Blatter
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Jan 1, 2021·Journal of Molecular and Cellular Cardiology·Jozefina SzlovákNorbert Nagy

Related Concepts

SEA 0400
Aniline Compounds
Metazoa
Cardiac Arrhythmia
Calcium
Cavia porcellus
Cardiac Conduction System
Resting Potentials
Diphenyl Oxides
Sarcoplasmic Reticulum

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