Related Experiment Video

Updated: Jun 5, 2026

Mechanical Stimulation-induced Calcium Wave Propagation in Cell Monolayers: The Example of Bovine Corneal Endothelial Cells
10:46

Mechanical Stimulation-induced Calcium Wave Propagation in Cell Monolayers: The Example of Bovine Corneal Endothelial Cells

Published on: July 16, 2013

Pharmacological modulation of connexin-formed channels in cardiac pathophysiology

Elke De Vuyst1, Kerstin Boengler, Gudrun Antoons

  • 1Department of Basic Medical Sciences - Physiology group, Faculty of Medicine and Health Sciences, Ghent University, Belgium.

British Journal of Pharmacology
|January 27, 2011
PubMed

Insights

New drugs targeting cardiac gap junctions improve electrical coordination and reduce arrhythmia risk. These compounds enhance communication between heart cells without causing proarrhythmic side effects, offering promise for treating ischaemic cardiomyopathy.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Pharmacology

Background:

  • Cardiac electrical activity relies on gap junctions at cardiomyocyte intercalated discs.
  • Impaired gap junction communication contributes to re-entry arrhythmias post-myocardial ischaemia.
  • Current antiarrhythmic drugs have limited efficacy and side effects.

Purpose of the Study:

  • To review compounds that enhance gap junctional communication for novel antiarrhythmic therapy.
  • To explore agents that inhibit connexin 43 (Cx43) hemichannels to protect cardiomyocytes during ischaemia/reperfusion.
  • To identify drugs with improved safety profiles and reduced proarrhythmic potential.

Main Methods:

  • Review of scientific literature on gap junction modulators.
  • Focus on compounds including antiarrhythmic peptide (AAP), AAP10, ZP123, GAP-134, RXP-E, Gap 26, and Gap 27.
  • Analysis of effects on ion channels and clinical safety data.

Main Results:

  • Several compounds increase gap junctional communication, enhancing conduction velocity and reducing arrhythmia risk.
  • Some agents inhibit Cx43 hemichannels, limiting ischaemia/reperfusion injury.
  • Discussed compounds do not affect Na+, Ca2+, and K+ channels, avoiding proarrhythmic effects.
  • GAP-134, RXP-E, Gap 26, and Gap 27 show favorable safety profiles, with GAP-134 confirmed in Phase I trials.

Conclusions:

  • Compounds that modulate gap junction communication represent a promising new class of antiarrhythmic drugs.
  • These agents offer potential for treating arrhythmias in ischaemic cardiomyopathy with improved safety.
  • Targeting gap junctions and hemichannels provides a dual approach to cardiac protection and rhythm management.

More Related Videos

Determination of the Relative Cell Surface and Total Expression of Recombinant Ion Channels Using Flow Cytometry11:32

Determination of the Relative Cell Surface and Total Expression of Recombinant Ion Channels Using Flow Cytometry

Published on: September 28, 2016

Microdissection and Immunofluorescence Staining of Myocardial Sleeves in Murine Pulmonary Veins08:52

Microdissection and Immunofluorescence Staining of Myocardial Sleeves in Murine Pulmonary Veins

Published on: November 21, 2023

Related Concept Videos

Gap Junctions01:37

Gap Junctions

Multicellular organisms employ a variety of ways for cells to communicate with each other. Gap junctions are specialized proteins that form pores between neighboring cells in animals, connecting the cytoplasm between the two, and allowing for the exchange of molecules and ions. They are found in a wide range of invertebrate and vertebrate species, mediate numerous functions including cell differentiation and development, and are associated with numerous human diseases, including cardiac and...
Gap Junctions01:27

Gap Junctions

The cytoplasm of adjacent animal cells can exchange small molecules, ions, and secondary messengers via the communication channels which form the gap junctions. These junctions comprise a few hundred to thousands of molecular channels, each made of two halves, called the connexon hemichannel. A connexon is a hexamer of six transmembrane connexin proteins, which assemble radially, thus forming a pore or channel in the center. One connexon hemichannel docks with a corresponding connexon on the...
G-Protein Gated Ion Channels01:21

G-Protein Gated Ion Channels

GPCRs are primarily responsible for our sense of smell, taste, and vision.  The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
Sensory organs,...
Mechanism of Cardiac Arrhythmias01:28

Mechanism of Cardiac Arrhythmias

Arrhythmias are irregular heart rhythms occurring when the heart's electrical impulses become abnormal. These disturbances can lead to various symptoms, depending on their severity and the underlying cause. Some common factors contributing to arrhythmias include hypoxia, ischemia, electrolyte imbalances, excessive catecholamine exposure, drug toxicity, and muscle overstretching. Arrhythmias can be classified into two main types based on the rate and site of origin of abnormal heart rhythms.
Pathophysiology of Cardiac Performance01:29

Pathophysiology of Cardiac Performance

Typical heart performance is influenced by heart rate, rhythm, myocardial contraction, and metabolism or blood flow. The cardiac muscle exhibits distinct electrophysiological features, including pacemaker activity and calcium channel control, which play a vital role in the heart's response to various drugs. The autonomic nervous system, comprising the sympathetic and parasympathetic branches, regulates heart rate. Sympathetic activation increases heart rate, while parasympathetic activation...
Electrophysiology of Normal Cardiac Rhythm01:19

Electrophysiology of Normal Cardiac Rhythm

The normal cardiac rhythm is a synchronized electrical activity that facilitates the regular and coordinated contraction of the heart muscle. This process is essential for efficient blood circulation throughout the body. The fundamental elements involved in establishing and maintaining this rhythm include the unique electrical properties of cardiac muscle cells, the sinoatrial (SA) node's pacemaker function, the specialized conducting system, and the ionic mechanisms underlying each phase of...