Related Experiment Video

Updated: Jul 5, 2025

Voltage-Dependent Potassium Current Recording on H9c2 Cardiomyocytes via the Whole-Cell Patch-Clamp Technique
08:11

Voltage-Dependent Potassium Current Recording on H9c2 Cardiomyocytes via the Whole-Cell Patch-Clamp Technique

Published on: November 11, 2022

2.8K

Amiodarone Advances the Apoptosis of Cardiomyocytes by Repressing Sigmar1 Expression and Blocking KCNH2-related

Huiqing Liang1, Huixian Li1, Fangjiang Li1

  • 1Department of Cardiology, The First Affiliated Hospital of Hebei North University, Zhangjiakou, China.

Current Molecular Medicine
|January 11, 2024
PubMed

Insights

Amiodarone induces cardiomyocyte apoptosis by reducing Sigmar1 expression and inhibiting KCNH2 channels, contributing to heart failure. Upregulating Sigmar1 can reverse these toxic effects.

Area of Science:

  • Cardiovascular Biology
  • Mitochondrial Medicine
  • Pharmacology

Background:

  • Heart failure (HF) is a complex cardiovascular disease.
  • Mitochondrial dysfunction and cardiomyocyte apoptosis are key pathological mechanisms in HF.

Purpose of the Study:

  • To investigate the anti-arrhythmic drug amiodarone's mechanism of action on mitochondrial toxicity in cardiomyocytes.
  • To elucidate the role of Sigmar1 and KCNH2 in amiodarone-induced cardiotoxicity.

Main Methods:

  • Cell viability was assessed using MTT assays in H9c2 cells treated with amiodarone.
  • Apoptosis, reactive oxygen species (ROS) levels, and mitochondrial membrane potential (MMP) were measured.
  • Sigmar1 and KCNH2 (potassium voltage-gated channel subfamily H member 2) expression levels were analyzed via qRT-PCR and Western blot.

Main Results:

  • Amiodarone reduced H9c2 cell viability (IC50 = 2.62 μM) and suppressed Sigmar1 expression.
  • Amiodarone triggered apoptosis, increased ROS production, and caused mitochondrial depolarization.
  • Sigmar1 upregulation counteracted amiodarone's toxic effects, while KCNH2 silencing partially reversed these outcomes.

Conclusions:

  • Amiodarone promotes H9c2 cell apoptosis by inhibiting Sigmar1 expression.
  • The drug's cardiotoxicity involves the blockade of KCNH2-related potassium channels.
  • Targeting Sigmar1 may offer a therapeutic strategy against amiodarone-induced mitochondrial damage.
Abstract

Keywords:
AmiodaroneH9c2 cells.Sigmar1heart failurepotassiumsubfamily H member 2voltage-gated cannel

More Related Videos

Contractions of Human-iPSC-derived Cardiomyocyte Syncytia Measured with a Ca-sensitive Fluorescent Dye in Temperature-controlled 384-well Plates07:42

Contractions of Human-iPSC-derived Cardiomyocyte Syncytia Measured with a Ca-sensitive Fluorescent Dye in Temperature-controlled 384-well Plates

Published on: October 18, 2018

6.3K
Isolation of Human Atrial Myocytes for Simultaneous Measurements of Ca2+ Transients and Membrane Currents10:53

Isolation of Human Atrial Myocytes for Simultaneous Measurements of Ca2+ Transients and Membrane Currents

Published on: July 3, 2013

20.4K

Related Concept Videos

Antiarrhythmic Drugs: Class III Agents as Potassium Channel Blockers01:12

Antiarrhythmic Drugs: Class III Agents as Potassium Channel Blockers

Class III antiarrhythmic drugs are a group of medications that can prolong action potentials in the heart. They achieve this by blocking potassium channels or enhancing inward currents from sodium channels. However, these drugs have a unique property of "reverse use-dependence," which is most pronounced at slower heart rates and can lead to torsades de pointes—a specific type of arrhythmia. However, it is essential to note that excessive QT interval prolongation—a measure of...
1.0K
Antiarrhythmic Drugs: Class I Agents as Sodium Channel Blockers01:22

Antiarrhythmic Drugs: Class I Agents as Sodium Channel Blockers

Class I antiarrhythmic drugs are used to treat various types of arrhythmias or irregular heart rhythms. These drugs block the sodium (Na+) channels in the cardiac cells, thereby affecting the movement of electrical impulses across the heart. Class I antiarrhythmic drugs are divided into three subgroups: Class IA, Class IB, and Class IC, each with distinct mechanisms of action and effects on the heart.
Class 1A Antiarrhythmic Drugs: These drugs work by moderately blocking sodium channels,...
1.4K
Heart Failure Drugs: Inotropic Agents01:26

Heart Failure Drugs: Inotropic Agents

Positive inotropic agents are commonly used as the first line of treatment for heart failure. One such agent is digoxin, derived from the genus Digitalis, which has been known for centuries but effectively utilized since 1785. However, these cardiac glycosides can have potentially toxic effects due to their mechanism of action, which involves inhibiting Na+/K+-ATPase and increasing contractility. Digoxin is absorbed orally and distributed in various tissues, including the CNS. It has a long...
591
Antiarrhythmic Drugs: Class IV Agents as Calcium Channel Blockers01:20

Antiarrhythmic Drugs: Class IV Agents as Calcium Channel Blockers

Class IV antiarrhythmic drugs, such as verapamil and diltiazem, block calcium channels. They primarily affect the heart, slowing the conduction in calcium-dependent tissues like the SA and AV nodes. These drugs manage reentrant supraventricular tachycardia (SVT) and reduce ventricular rate in atrial flutter/fibrillation.
Verapamil, a calcium channel blocker, inhibits calcium movement across myocardial cell membranes and vascular smooth muscle. This results in the dilation of coronary and...
836
Antiarrhythmic Drugs: Class II Agents as β-Adrenergic Blockers01:24

Antiarrhythmic Drugs: Class II Agents as β-Adrenergic Blockers

Adrenergic stimulation generally impacts cardiac rate and rhythm. Specifically, stimulation of the β-adrenoceptors triggers an increase in intracellular calcium ion influx and pacemaker currents, which may cause arrhythmias. Catecholamines like adrenaline also demonstrate β2-adrenoceptor-mediated hypokalemia, impacting cardiac action potential and disrupting the normal cardiac rhythm. Class II antiarrhythmic drugs are β-adrenoceptor antagonists or β-blockers, which...
746
Heart Failure Drugs: Inhibitors of Renin-Angiotensin System01:26

Heart Failure Drugs: Inhibitors of Renin-Angiotensin System

The activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) contributes to cardiac remodeling, and inhibiting the RAAS is a pharmacological target in heart failure management. As a result, neurohumoral modulation is a crucial treatment principle for managing heart failure. This approach involves using medications like ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers, mineralocorticoid receptor antagonists (MRAs), and neutral...
432