Luo Yingchun, Ma Wenbo, Kang Qi, Pan Han, Shi Ling, Ma Jiudong, Song Jiahui, Gong Dongmei, Kang Kai, Jin Xuexin
The Key Laboratory of Cardiovascular Disease Acousto-Optic Electromagnetic Diagnosis and Treatment in Heilongjiang Province, The First Affiliated Hospital of Harbin Medical University, Harbin 150081, China.
Department of State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin 150081, China.
Acta Biochim Biophys Sin (Shanghai). 2025 Mar 19;57(7):1115-1124. doi: 10.3724/abbs.2025018.
Diabetes mellitus (DM) is a risk factor for the development of atrial fibrillation (AF). The action potential duration (APD) has been demonstrated to be prolonged in the atrium of diabetic mice. In contrast, the APD is generally shortened in AF patients. It is unclear what change occurs in the atrial APD of diabetic patients. In this study, we explore the APD change of atrial myocytes from diabetic patients and the underlying molecular mechanisms. The whole-cell patch-clamp technique is used to detect single-cell electrical activity in diabetic and nondiabetic human samples. The results show that both APD and APD , the APD at 50% and 90% repolarization, are increased in diabetic patients compared with those in nondiabetic controls. The density of late sodium current ( ) in the atrial myocytes of diabetic patients is greater than that in the myocytes of nondiabetic patients. The expression of receptor for advanced glycation end products (RAGE) is increased in the atria of diabetic patients. In cultured HL-1 cells, high glucose (HG) treatment increases , and the expression of RAGE prolongs APD. The siRNA-mediated knockdown of reduces the and shortens the APD. The APD is prolonged in the atria of diabetic patients because of the upregulation of RAGE and the subsequent increase in . Our findings provide novel insights into atrial electrical remodeling in diabetic patients.
糖尿病（DM）是心房颤动（AF）发生的一个风险因素。已证实糖尿病小鼠心房的动作电位时程（APD）延长。相比之下，AF患者的APD通常缩短。目前尚不清楚糖尿病患者心房的APD会发生何种变化。在本研究中，我们探究了糖尿病患者心房肌细胞的APD变化及其潜在的分子机制。采用全细胞膜片钳技术检测糖尿病和非糖尿病人体样本中的单细胞电活动。结果显示，与非糖尿病对照组相比，糖尿病患者的APD以及复极化50%和90%时的APD均增加。糖尿病患者心房肌细胞中晚钠电流（ ）的密度大于非糖尿病患者肌细胞中的密度。糖尿病患者心房中晚期糖基化终末产物受体（RAGE）的表达增加。在培养的HL-1细胞中，高糖（HG）处理会增加 ，且RAGE的表达会延长APD。小干扰RNA（siRNA）介导的 敲低会降低 并缩短APD。由于RAGE上调及随后 的增加，糖尿病患者心房的APD延长。我们的研究结果为糖尿病患者心房电重构提供了新的见解。
