Quantitative analysis of potassium channel mRNA expression in atrial and ventricular muscle of rats.

Abstract

The expression of 15 different potassium channel genes in rat atrial and ventricular muscle was quantitatively compared by use of an RNase protection assay. Of these genes, only five, Kv1.2, Kv1.4, Kv1.5, Kv2.1, and Kv4.2, were expressed at significant levels in cardiac muscle. In comparisons of atrial and ventricular RNA samples, transcripts from the Kv1.2 and Kv4.2 genes showed the largest differences in relative abundance. There was an approximately twofold decrease in total Kv4 subfamily mRNA expression in atrial muscle relative to ventricular muscle and a 70% increase in total Kv1 subfamily mRNA. Variation of potassium channel mRNA expression within the left ventricular wall was also examined. There was a large gradient of Kv4.2 expression across the ventricular wall, and Kv4.2 expression in epicardial muscle was more than eight times higher than in papillary muscle. Other potassium channel genes were expressed at relatively uniform levels across the ventricular wall. The results suggest that transcriptional regulation makes a significant contribution to the control of potassium channel expression in cardiac muscle and to the variation of the electrophysiological phenotype of myocytes from different regions of the myocardium.

Myocardial infarction in rat eliminates regional heterogeneity of AP profiles,ItoK+currents, and [Ca2+]itransients

“…These results are consistent with a previous study showing that I sus is significantly reduced in the left ventricular endocardium after shortterm infarction (61). The molecular correlates of I sus remains uncertain, but three candidate K ϩ channel genes (Kv1.2, Kv1.5, and Kv2.1) are expressed in the rat heart (16,51,53). In the right ventricle, RNase protection assays (data not shown) revealed that the percentage reductions in mRNA levels after MI did not reach significance for Kv1.2, (23.7 Ϯ 15.3%, n ϭ 5, P ϭ 0.19), Kv1.5 (22.4 Ϯ 11.4%, n ϭ 5, P ϭ 0.11) or Kv2.1 (27.0 Ϯ 9.8%, n ϭ 5, P ϭ 0.06) genes.…”

“…To investigate the molecular basis for the changes in I to density, we examined the expression of Kv4.2, Kv4.3, and Kv1.4␣ subunits, which represent candidate voltage-dependent K ϩ channels encoding for I tolike currents previously shown to be expressed in rat heart (16). Figure 4 shows typical Western blots for Kv4.2, Kv4.3, and Kv1.4.…”

“…right ventricle; septum; heart disease; contraction THERE ARE MARKED DIFFERENCES in the action potential duration (APD) in different regions of the mammalian ventricle (4,15,18,39,58). This electrical heterogeneity in normal myocardium correlates with regional differences in the Ca 2ϩ -independent transient outward K ϩ current density (I to ) (5,15,18,34,35,43) as well as in gene expression of K ϩ channels (8,16,58). APD prolongation and reductions in I to density occur in rat heart after left anterior descending coronary artery ligation (2, 43, 58), aortic banding (5, 22, 55), as well as after treatment with either catecholamine (11) or monocrotaline (32, 33).…”

Long Noncoding RNA Kcna2 Antisense RNA Contributes to Ventricular Arrhythmias via Silencing Kcna2 in Rats With Congestive Heart Failure

“…There are >15 different potassium channel genes that have been quantitatively demonstrated to exist in rat atrial and ventricular muscles, with Kcna2, kv1.4, kv1.5, kv2.1, and kv4.2 being expressed at significant levels 7, 27. Western blot analyses of atrial and ventricular membrane proteins confirmed the presence of Kcna2 at 75 kDa in adult rat heart membranes 8.…”

“…Delayed rectifier potassium channels are important for controlling the repolarization of several ion species in the heart, and decreases in the delayed rectifier potassium current (I K ) in heart failure results in action potential (AP) prolongation, which is an important contributor to the development of ventricular arrhythmias 4, 5, 6. Kcna2, also known as Kv1.2, which is a subunit of the voltage‐gated shaker channel family, is one of the dominant ion channels in cardiac muscle and encodes I K 7, 8. The expression levels of myocardial Kcna2 are decreased in hypertrophic cardiac tissue, senescent hearts, diabetic hearts, and patients with obesity‐induced cardiomyopathy,9, 10, 11, 12 indicating that Kcna2 might be a key regulator of ventricular arrhythmias in CHF.…”