Electrophysiological properties vary in different regions of the heart, which is essential for effective cardiac function. Increasing evidence suggests that cardiac electrical heterogeneity is attributable to regional variability in distribution of ion channel and related genes. Dramatic progress in genomics has led to the discovery of a large number of ion channel genes; how these genes are expressed in specific regions of the heart and function in relation to its physiological function is largely unknown.

Hearts were excised from 20-25 g adult C57BL mice after humane killing by cervical dislocation. Total RNA was prepared from sinoatrial node (SAN), atrioventricular node (AVN), atrium and ventricles as described by Wittwer et al. (2002). Mouse Known Gene Array slides of 7.5 K (provided by the MRC HGMP Resource Centre) were used to identify the ion channel genes expressed in different regions of mouse heart. Amplification of cDNA by SMART was described by Vernon et al. (2000); labelling and hybridisation of cDNA were described by Smith et al. (2003). Reproducibility of signals is controlled by independent repeat hybridisations using different RNAs, colour swap and duplicate spots on the same array.

We have compared relative expression levels of ~500 channel and related genes in SAN, AVN, atrium and ventricle. Our preliminary results showed that there are regional differences in channel gene expression in murine heart. Channel genes Kcnj1, Kcnj8, Kcnj10, Kcna5, and Kcnh2, Scn8a and Scn1b and Hcn4 are highly expressed in nodal tissue (SAN/AVN), while channel genes Kcnj16, Kcna4, Kcnb1 and Gja1 (Cx43) are more highly expressed in muscle regions. In the profile of all genes, we found more differentially expressed genes between nodal and muscle regions, than between the two nodal regions. The gene expression profile between SAN and AVN is similar; this could be due to the functional and structural similarities between these two nodal regions. Further experiments using real time PCR and Western blot have been planned to validate these results.

This work was supported by The Wellcome Trust.