In the heart, gap junctions play an important role in impulse conduction. Studies over the last decade have revealed that gap junctions are encoded by a multigene family known as the connexins. There are at least 15 connexin genes in the vertebrate genome. 1 Connexins have been referred to by 2 nomenclature systems, either according to the molecular weight of the protein or by its class as determined by protein sequence. 1, 2 The molecular weight designation will be used here in conformity with the study by Kirchhoff et al3 in this issue of Circulation Research.

In the heart, there are 3 major connexin isotypes expressed: connexin (Cx) 43 (α1 connexin), Cx45 (α6 connexin), and Cx40 (α5 connexin). Each of these connexins exhibits different channel properties and is regulated by different gating mechanisms. Cx43 is the only connexin known to be expressed in the adult working myocardium, 4 although a recent report suggests that Cx37 (α6 connexin) also may be present. 5 In the specialized conductive tissue of the heart, Cx45 is found in the atrioventricular node and adjoining His bundles. 6 This connexin isotype forms voltage-sensitive channels with very low conductance. 7 In contrast, Cx40, which generates channels with high conductance, 8 is expressed in the fastconducting tissues of the His-Purkinje system, being nested within the Cx45 expression domain (Figure). 9, 10 In the Purkinje fibers of the peripheral conductive tissue, Cx43 is coexpressed with Cx40 (Figure). 9 It is hypothesized that this compartmentalized expression of connexins may provide for the orderly and sequential spread of activation from the atrial to ventricular chamber. 9–11 Thus, expression of Cx45 in the atrioventricular node and His bundle may electrically insulate the central conductive tissues from the working myocardium. In contrast, Cx40 may allow rapid impulse propagation to distal parts of the conduction system, where Cx43 may additionally facilitate coupling to the surrounding working myocytes.