DIFFERENTIAL EXPRESSION OF GAP JUNCTION PROTEINS IN THE CANINE SINUS NODE

Electrical coupling of pacemaker cells at gap junctions appears to pla y an important role in sinus node function. Although the major cardiac gap junction protein, connexin43 (Cx43), is expressed abundantly in a trial and ventricular muscle, its expression in the sinus node has bee n a subject of controversy. The objectives of the present study were t o determine whether Cx43 is expressed by sinus node myocytes, to chara cterize the spectrum of connexin expression phenotypes in sinus node p acemaker cells, and to define the spatial distribution of different co nnexin phenotypes in the intact sinus node. to fulfill these objective s, we performed high-resolution immunohistochemical analysis of disagg regated adult canine sinus node preparations. Using enhanced tissue pr eservation and antigen retrieval techniques, we also performed immunoh istochemical studies on sections of intact canine sinus node tissue. A nalysis of disaggregated sinus node preparations revealed three popula tions of pacemaker cells distinguished on the basis of connexin immuno histochemical phenotype: approximate to 55% of cells expressed only co nnexin40 (Cx40); 30% to 35% of cells expressed Cx43, connexin45 (Cx45) , and Cx40; and the remaining cells had no detectable connexin express ion. In immunostained sections of intact sinus node, Cx43- and Cx45-po sitive cells were limited in their distribution and were observed in d iscrete bundles that appeared to abut atrial myocytes. In contrast, Cx 40 immunoreactive signal was widely distributed in the sinus node regi on. These results indicate that subsets of pacemaker cells express dis tinct connexin phenotypes. Differential expression of connexins could create regions within the sinus node with different conduction propert ies, thereby contributing to the nonuniform conduction properties seen in this tissue.