Related Experiment Video

Updated: Jun 21, 2026

Isolation of Human Atrial Myocytes for Simultaneous Measurements of Ca2+ Transients and Membrane Currents
10:53

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

Published on: July 3, 2013

The negative inotropic action of canrenone is mediated by L-type calcium current blockade and reduced intracellular

A R Costa1, L B Torres, E Medei

  • 1Cardiology Division, Department of Medicine, Federal University of São Paulo (UNIFESP), São Paulo, Brazil. andrea.costa@case.edu

British Journal of Pharmacology
|August 12, 2009
PubMed

Insights

Canrenone, a spironolactone metabolite, impairs heart muscle contractility by reducing calcium channel activity and sarcoplasmic reticulum calcium stores. These findings clarify mechanisms of spironolactone

Area of Science:

  • Cardiovascular Physiology
  • Molecular Pharmacology
  • Cardiac Electrophysiology

Background:

  • Spironolactone therapy benefits heart failure patients, but its mechanisms require elucidation.
  • Canrenone is the primary active metabolite of spironolactone.
  • Understanding canrenone's effects on cardiac function is crucial for optimizing heart failure treatment.

Purpose of the Study:

  • To investigate the impact of canrenone on myocardial contractility.
  • To analyze canrenone's effects on intracellular calcium handling in cardiac cells.
  • To elucidate the cellular mechanisms underlying spironolactone's therapeutic effects in heart failure.

Main Methods:

  • Isolated rat papillary muscles were used to assess contractility via force transducers.
  • Cardiomyocytes were utilized to measure calcium transients using fluorescence techniques.
  • Electrophysiological methods were employed to evaluate calcium fluxes and L-type calcium channel currents.

Main Results:

  • Canrenone significantly reduced developed tension and rates of tension change in papillary muscles.
  • In cardiomyocytes, canrenone decreased cell shortening and L-type calcium channel current.
  • Canrenone diminished sarcoplasmic reticulum calcium content and intracellular calcium transient amplitude.

Conclusions:

  • Canrenone exerts a negative inotropic effect on the heart.
  • Reduced L-type calcium channel current and impaired calcium handling contribute to canrenone's cardiac effects.
  • These findings provide mechanistic insights into spironolactone's benefits in heart failure management.
Abstract

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

Preparation of Human Myocardial Tissue for Long-Term Cultivation10:58

Preparation of Human Myocardial Tissue for Long-Term Cultivation

Published on: June 2, 2022

Related Concept Videos

Antihypertensive Drugs: Action of Calcium Channel Blockers01:18

Antihypertensive Drugs: Action of Calcium Channel Blockers

Calcium ions are essential to contract smooth muscle cells in blood vessels. They enter these cells through voltage-dependent calcium channels, specifically L-type calcium channels in the cell membrane. These L-type calcium channels are integral to the excitation-contraction coupling process in smooth muscle. When a stimulus is received by smooth muscle cells, their membrane depolarizes. This alteration in membrane potential instigates the opening of L-type calcium channels. As a result,...
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...
Antianginal Drugs: Calcium Channel Blockers and Ranolazine01:25

Antianginal Drugs: Calcium Channel Blockers and Ranolazine

Angina pectoris, a primary symptom of ischemic heart disease, requires careful pharmacological interventions. In this context, calcium channel blockers (CCBs) and ranolazine have emerged as crucial pharmacotherapeutic agents, providing deep insights into the complexities of angina management.
CCBs, a diverse class that includes dihydropyridines (nifedipine) and diphenylalkylamines (verapamil and diltiazem), exert their effect by blocking calcium channels in cardiac and smooth muscle cells. This...
Ligand-Gated Ion Channel Receptor: Gating Mechanism01:30

Ligand-Gated Ion Channel Receptor: Gating Mechanism

Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
Nondepolarizing (Competitive) Neuromuscular Blockers: Mechanism of Action01:17

Nondepolarizing (Competitive) Neuromuscular Blockers: Mechanism of Action

Nondepolarizing neuromuscular blockers induce paralysis by competitively blocking nicotinic acetylcholine receptors at the muscle end plate. Examples include pancuronium, mivacurium, vecuronium, and rocuronium. These quaternary ammonium derivatives are administered intravenously, are poorly absorbed, and are excreted via the kidneys.
Competitive antagonists prevent acetylcholine from binding to its receptor, inhibiting membrane depolarization. Without conformational changes or intrinsic...
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...