Imoto Keisuke, Sakai Yuho, Okada Muneyoshi, Otani Kosuke, Yamawaki Hideyuki
Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Higashi 23-35-1, Towada-shi, Aomori 034-8628, Japan.
J Vet Med Sci. 2021 Jul 10;83(6):997-1003. doi: 10.1292/jvms.21-0040. Epub 2021 Apr 29.
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) in isolated ventricular myocytes. Protein expression of cardiac voltage-gated Na channel (Na1.5) 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 in the isolated ventricular myocytes. POSTN-injection decreased Na1.5 expression in the isolated ventricles. It was confirmed that POSTN (1 µg/ml, 24 hr) decreased I and Na1.5 protein expression in neonatal rat ventricular myocytes. This study for the first time demonstrated that a single injection of POSTN in rats decreased I by suppressing Na1.5 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.
电生理特性的变化，如离子通道的表达和活性，与心力衰竭（HF）期间的心律失常发生密切相关。然而，HF中电重构的致病因素尚未确定。骨膜蛋白（POSTN）是一种基质细胞蛋白，在HF患者的心脏组织中含量增加。在本研究中，我们调查了单次注射POSTN是否会影响大鼠心室的电生理特性。雄性Wistar大鼠静脉注射重组大鼠POSTN（64μg/kg，24小时）后，记录心电图（ECG）。采用全细胞膜片钳技术测量分离的心室肌细胞的动作电位（AP）和钠电流（I）。通过蛋白质印迹法检测分离心室中心脏电压门控钠通道（Na1.5）的蛋白表达。在心电图中，注射POSTN后RS波高度显著增加。注射POSTN后，分离的心室肌细胞的AP峰值时间显著延迟，I降低。注射POSTN可降低分离心室中Na1.5的表达。证实POSTN（1μg/ml，24小时）可降低新生大鼠心室肌细胞的I和Na1.5蛋白表达。本研究首次证明，大鼠单次注射POSTN可通过抑制心室肌细胞中Na1.5的表达来降低I，这伴随着AP峰值时间的延长和心电图中RS波高度的增加。
