THE SPATIAL-DISTRIBUTION AND RELATIVE ABUNDANCE OF GAP-JUNCTIONAL CONNEXIN40 AND CONNEXIN43 CORRELATE TO FUNCTIONAL-PROPERTIES OF COMPONENTS OF THE CARDIAC ATRIOVENTRICULAR-CONDUCTION SYSTEM

Electrical coupling between heart muscle cells is mediated by speciali sed regions of sarcolemmal interaction termed gap junctions. In previo us work, we have demonstrated that connexin42, a recently identified g ap-junctional protein, is present in the specialised conduction tissue s of the avian heart. In the present study, the spatial distribution o f the mammalian homologue of this protein, connexin40, was examined us ing immunofluorescence, confocal scanning laser microscopy and quantit ative digital image analysis in order to determine whether a parallel distribution occurs in rat. Connexin40 was detected by immunofluoresce nce in all main components of the atrioventricular conduction system i ncluding the atrioventricular node, atrioventricular bundle, and Purki nje fibres. Quantitation revealed that levels of connexin40 immunofluo rescence increased along the axis of atrioventricular conduction, risi ng over 10-fold between atrioventricular node and atrioventricular bun dle and a further 10-fold between atrioventricular bundle and Purkinje fibres. Connexin40 and connexin43, the principal gap-junctional prote in of the mammalian heart, were co-localised within atrioventricular n odal tissues and Purkinje fibres. By applying a novel photobleach/doub le-labelling protocol, it was demonstrated that connexin40 and connexi n43 are colocalised in precisely the same Purkinje fibre myocytes. A m odel, integrating data on the spatial distribution and relative abunda nce of connexin40 and connexin43 in the heart, proposes how myocyte-ty pe-specific patterns of connexin isform expression account for the ele ctrical continuity of cardiac atrioventricular conduction.