Abstract
Cardiac remodeling is a necessary process in the context of physiological adaptation during normal growth according to the demand of alterations, including changes in contractility and beating rate. However, malfunctional remodeling due to pathological conditions is an ultimate disaster in disease pathogenesis, which leads to a poor outcome and high mortality [1]. Besides the cardiac enlargement of ventricular volume after myocardial infarction (MI), dysfunction due to electrophysiological remodeling such as a decrease in delayed rectifier potassium currents (IK) is a prominent feature showing reduced survival in patients with heart disease [2]. Cardiac inward rectifying potassium currents (Ik1) play an important role in shaping action potentials, which is a key character representing the electrical activity made by a multitude of various ion channels and transporters [3]. The cardiac IK1 stabilizes the resting membrane potential and is responsible for shaping the initial depolarization and final repolarization of the action potential [4, 5]. Indeed, infarction generally entails significant cellular and molecular remodeling in the left ventricle, resulting in functional and biochemical alterations of the myocardium due to the modulation of IK1 [2]. Therefore, focusing on a strategy to attenuate the pathogenic remodeling, such as decrease in IK1 after MI has been receiving increasing attention. Notably, a delayed rectifier potassium channel, Kir2.1, which is encoded by the KCNJ2 gene, has been studied because it has been demonstrated that Kir2.1 expression is decreased after MI [6]. Also, overexpression of Kir2.1 channel in embryonic stem cell-derived cardiomyocytes attenuates post-transplantation proarrhythmic risk in myocardial infarction [7]. Previously, studies have shown the mechanisms undergoing transcriptional modulation of Kir2.1 after myocardial infarction. For example, upregulation of microRNA-1 (miR-1) and consequent reduction of Kir2.1 is observed in rat ventricular myocytes in a rodent model of MI. This is due to the increase in serum response factor (SFR), a transcriptional activator of the miR-1 gene [8]. In the current issue of Cardiovascular Drugs and Therapy, Li et al. report evidence for kinase-dependent modulation of IK1 in anMI rodent model [9]. This work not only identifies a new potential target to attenuate the risk of heart failure after MI, but also provides additional information on the mechanisms of how valsartan, an angiotensin II type I receptor blocker attenuates the effect of MI. First, they induce the MI in male Wistar rats by ligation of the coronary artery, which upregulates casein kinase 2 (CK2) expression and downregulates Kir2.1 expression in myocytes in the left ventricle. In addition, in rat ventricular cells, CK2 overexpression leads to reduction of Kir2.1 expression. This effect is abolished by 4,5,6,7-Tetrabromobenzotriazole (TBB), a cellpermeable selective inhibitor of CK2, treatment. Also, this biochemical data is confirmed by electrophysiological data showing IK1 current density in cultured neonatal rat ventricular cardiomyocytes is decreased by CK2 overexpression and this effect is abolished by TBB treatment. Using an Electrophoretic mobility shift assay (EMSA), the regulation of the CK2 activity after MI was confirmed. Most of all, this provides the new insight that CK2 has an important role in MI-induced ion channel remodeling. Although it has been demonstrated that CK2 has an important role in modulating cardiac hypertrophy; for example, CK2 induces development of hypertrophic phenotypes in rat * Seungwoo Kang seungwoo.kang@rutgers.edu
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