Differential gene expression of cardiac chloride and potassium ion channels in human dilated non-ischemic cardiomyopathy

Purpose: Dilated Cardiomyopathy (DCM) may be induced by different etiologies, but it is known that ion-channel disruptions play an important role. The major ion channels involved in both the depolarization and repolarization of muscle cells are the ones that regulate sodium, potassium, calcium and chloride ion fluxes. The aim of the study is to evaluate the differential gene expression of cardiac chloride and potassium ion channels that represents two ways of ion-flux alterations in DCM patients, compared to normal subjects. Methods: Experimental material was taken from 42 explanted human hearts. The RNA of 31 heart samples from DCM (DCM, n=31) patients undergoing heart transplantation and control donors (CNT, n=11) was extracted to perform a microarray profiling. We also performed qRT-PCR and Western blot analysis. Results: We focused on the study of 4 ion channels related genes, since this functional category has not previously been studied. Two chloride (CLIC2, CLCN3) were down regulated (p<0.0001) and two potassium (KCNJ5, KCNJ8) were also down regulated (p<0.0001), in DCM. Validation of the results showed a high degree of consistency with microarray results. We determined whether gene expression changes resulted in alterations at the protein level. Moreover, we observed a significant inverse relationship between the expression of CLCN3 (r=-0.7, p<0.05), KCNJ5 (r=-0.7, p<0.05) and KCNJ8 (r=-0.7, p<0.05) and left ventricular end diastolic dimension in subjects with DCM. Conclusions: In this study we show that the expression of chloride and potassium-related genes is altered in HF of dilated non-ischemic origin. Furthermore, CLCN3, KCNJ5 and KCNJ8 mRNA levels are closely related with left ventricular end-diastolic dimension in subjects with DCM. These findings could provide a new base for therapeutic oriented studies.