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Mice lacking connexin40 have cardiac conduction abnormalities characteristic of atrioventricular block and bundle
A M Simon1, D A Goodenough, D L Paul
1Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Insights
Connexin40 (Cx40) gap junctions are crucial for rapid cardiac electrical conduction. Mice lacking Cx40 exhibit conduction abnormalities, highlighting their essential role in the His-Purkinje system.
Area of Science:
- Cardiovascular physiology
- Molecular cardiology
- Electrophysiology
Background:
- Cardiac muscle activation relies on the His-Purkinje system for coordinated excitation spread.
- Pathologies of this system are prevalent, particularly in the elderly, but their molecular underpinnings remain unclear.
- Gap junctions, formed by connexins, facilitate impulse propagation between specialized cardiac cells.
Purpose of the Study:
- To investigate the role of gap junction communication in cardiac conduction.
- To determine the necessity of connexin40 (Cx40) in the His-Purkinje system's function.
Main Methods:
- Generation of Cx40 knockout (null) mice.
- Electrocardiographic analysis of cardiac conduction in Cx40 null mice.
Main Results:
- Cx40 null mice displayed significant cardiac conduction abnormalities.
- These abnormalities were characterized by first-degree atrioventricular block and bundle branch block.
- The findings indicate impaired impulse propagation in the His-Purkinje system.
Conclusions:
- Gap junctions, specifically those involving Cx40, are essential for rapid impulse conduction within the His-Purkinje system.
- Cx40 plays a critical role in maintaining normal cardiac electrical activity.
- Defects in Cx40-mediated gap junction communication can lead to significant cardiac conduction disorders.
Abstract:
Activation of cardiac muscle is mediated by the His-Purkinje system, a discrete pathway containing fast-conducting cells (Purkinje fibers) which coordinate the spread of excitation from the atrioventricular node (AV node) to ventricular myocardium [1]. Although pathologies of this specialized conduction system are common in humans, especially among the elderly [2], their molecular bases have not been defined. Gap junctions are present at appositions between Purkinje fibers and could provide a mechanism for propagating impulses between these cells [3]. Studies of the expression of connexins - the family of proteins from which gap junctions are formed - reveal that connexin40 (Cx40) is prominent in the conduction system [4]. In order to study the role of gap junction communication in cardiac conduction, we generated mice that lack Cx40. Using electrocardiographic analysis, we show that Cx40 null mice have cardiac conduction abnormalities characteristic of first-degree atrioventricular block with associated bundle branch block. Thus, gap junctions are essential for the rapid conduction of impulses in the His-Purkinje system.