Abstract
The ionic mechanisms underlying pacemaker activity have been extensively studied in the sinoatrial (SA) node, but little is known about the molecular basis of ionic currents. The aim of this study was to evaluate mRNA expression for ion channels, connexins and Ca2+-handling proteins using quantitative PCR and to visualize the distribution of these transcripts using in situ hybridization in and around the rabbit SA node. Quantitative PCR showed that there were significant differences in the abundance of 60% of the 30 mRNAs studied in different tissues (SA node center, SA node periphery and atrial muscle). Grouping analysis of the PCR data identified two significantly different clusters: mRNAs tended to increase (Cx45, Nav1.1, Cav1.3, HCN1, HCN4, Kv4.2, ERG, KvLQT1, Kir2.2 and Kir3.1) and those tended to decrease (Cx43, Cx40, RYR2, SERCA2a, Nav1.5, Cav1.2, Kv1.4, Kv4.3, KChIP2, Kv1.5, minK, Kir2.1 and Kir6.2) from the atrial muscle to the center of the SA node. The mRNA expression profiles of the center and the periphery of the SA node were similar but there were significant differences for some transcripts (e.g. Cav1.3, HCN1 and HCN4). In situ hybridization confirmed these regional differences in the mRNA expression pattern. This study shows a complex variation in the expression of ion channel mRNAs from the atrial muscle to the SA node, which may be important in the functional organization of the SA node as a physiological and dependable pacemaker of the heart. [J Physiol Sci. 2006;56 Suppl:S124]
