A single injection of periostin decreases cardiac voltage-gated Na⁺ channel in rat ventricles

Abstract

Changes in electrophysiological properties, such as ion channel expression and activity, are closely related to arrhythmogenesis during heart failure (HF). However, a causative factor for the electrical remodeling in HF has not been determined. Periostin (POSTN), a matricellular protein, is increased in heart tissues of patients with HF. In the present study, we investigated whether a single injection of POSTN affects the electrophysiological properties in rat ventricles. After male Wistar rats were intravenously injected with recombinant rat POSTN (64 µg/kg, 24 hr), electrocardiogram (ECG) was recorded. Whole-cell patch clamp was performed to measure action potential (AP) and Na + current ( I Na ) in isolated ventricular myocytes. Protein expression of cardiac voltage-gated Na + channel (Na V 1.5) in isolated ventricles was examined by Western blotting. In ECG, POSTN-injection significantly increased RS height. POSTN-injection significantly delayed time to peak in AP and decreased I Na in the isolated ventricular myocytes. POSTN-injection decreased Na V 1.5 expression in the isolated ventricles. It was confirmed that POSTN (1 µg/ml, 24 hr) decreased I Na and Na V 1.5 protein expression in neonatal rat ventricular myocytes. This study for the first time demonstrated that a single injection of POSTN in rats decreased I Na by suppressing Na V 1.5 expression in the ventricular myocytes, which was accompanied by a prolongation of time to peak in AP and an increase of RS height in ECG.

Progress on role of ion channels of cardiac fibroblasts in fibrosis

“…RT-qPCR, immunofluorescence and pharmacological experiment also show the same results ( Dobrev et al, 2012 ). I Na is mainly detected by Nav1.5, which is the first time to show I Na in human atrial MFs ( Imoto et al, 2021 ). As a potential marker of human atrial MFs, I Na can promote the electrophysiological separation of patients’ atrial fibroblasts and MFs, which may control the transformation of fibroblasts to MFs secreting ECM.…”