MICE LACKING CONNEXIN40 HAVE CARDIAC CONDUCTION ABNORMALITIES CHARACTERISTIC OF ATRIOVENTRICULAR-BLOCK AND BUNDLE-BRANCH BLOCK

Activation of cardiac muscle is mediated by the His-Purkinje system, a discrete pathway containing fast-conducting cells (Purkinje fibers) w hich coordinate the spread of excitation from the atrioventricular nod e (AV node) to ventricular myocardium [1], Although pathologies of thi s specialized conduction system are common in humans, especially among the elderly [2], their molecular bases have not been defined, Gap jun ctions are present at appositions between Purkinje fibers and could pr ovide a mechanism for propagating impulses between these cells [3], St udies of the expression of connexins - the family of proteins from whi ch gap junctions are formed - reveal that connexin40 (Cx40) is promine nt in the conduction system [4], In order to study the role of gap jun ction communication in cardiac conduction, we generated mice that lack Cx40, Using electrocardiographic analysis, we show that Cx40 null mic e 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 H is-Purkinje system.