Effects of amiodarone on rodent ventricular cardiomyocytes: Novel perspectives from a cellular model of Long QT Syndrome Type 3.

Abstract:

AIMS:Amiodarone (AMIO) is currently used in medical practice to reverse ventricular tachycardia. Here we determine the effects of AMIO in the electromechanical properties of isolated left ventricle myocyte (LVM) from mice and guinea pig and in a cellular model of Long QT Syndrome Type 3 (LQTS-3) using anemone neurotoxin 2 (ATX II), which induces increase of late sodium current in LVM. MAIN METHODS AND KEY FINDINGS:Using patch-clamp technique, fluorescence imaging to detect cellular Ca2+ transient and sarcomere detection systems we evaluate the effect of AMIO in healthy LVM. AMIO produced a significant reduction in the percentage of sarcomere shortening (0.1, 1 and 10 μM) in a range of pacing frequencies, however, without significant attenuation of Ca2+ transient. Also, 10 μM of AMIO caused the opposite effect on action potential repolarization of mouse and guinea pig LVM. When LVM from mouse and guinea pig were paced in a range of pacing frequencies and exposed to ATX (10 nM), AMIO (10 μM) was only able to abrogate electromechanical arrhythmias in LVM from guinea pig at lower pacing frequency. SIGNIFICANCE:AMIO has negative inotropic effect with opposite effect on action potential waveform in mouse and guinea pig LVM. Furthermore, the antiarrhythmic action of AMIO in LQTS-3 is species and frequency-dependent, which indicates that AMIO may be beneficial for some types of arrhythmias related to late sodium current.

journal_name

Life Sci

journal_title

Life sciences

authors

Beserra SS,Santos-Miranda A,Sarmento JO,Miranda VM,Roman-Campos D

doi

10.1016/j.lfs.2020.117814

subject

Has Abstract

pub_date

2020-08-15 00:00:00

pages

117814

eissn

0024-3205

issn

1879-0631

pii

S0024-3205(20)30563-4

journal_volume

255

pub_type

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