Work

Atrial APD prolongation caused by the upregulation of RAGE and subsequent INaL increase in diabetic patients

Year: 2025

Type: article

Abstract: 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 APD50 and APD90, the APD at both 50% and 90% repolarization, are increased in diabetic patients compared with nondiabetic controls. The density of INaL in the atrial myocytes of diabetic patients is greater than that in the myocytes of nondiabetic patients. The expression of RAGE is increased in the atria of diabetic patients. In cultured HL-1 cells, high glucose (HG) treatment increases INaL, and the expression of the receptor for advanced glycation end products (RAGE) prolongs APD. The siRNA-mediated knockdown of RAGE reduces the late sodium current 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 INaL. Our findings provide novel insights into atrial electrical remodeling in diabetic patients.

Source: Acta Biochimica et Biophysica Sinica

DOI: 10.3724/abbs.2025018