The electrophysiological effects of Tongyang Huoxue granules on the ignition phase during hypoxia/reoxygenation injury in sinoatrial node cells.

Abstract

This study was undertaken to explore the potential therapeutic effects of Tongyang Huoxue Granules (TYHX) on sinoatrial node (SAN) dysfunction, a cardiac disorder characterized by impaired impulse generation or conduction. The research question addressed whether TYHX could positively influence SAN ion channel function, specifically targeting the sodium-calcium exchanger (I NCX) and L-type calcium channel (I CaL) of the SAN. Sinoatrial node cells (SANCs) were isolated and cultured from neonatal Japanese big-eared white rabbits within 24h of birth. The study encompassed five groups: Control, H/R (hypoxia/reoxygenation), H/R+100μg/mL TYHX, H/R+200μg/mL TYHX, and H/R+400μg/mL TYHX. The H/R model, simulating hypoxia/reoxygenation stress, was induced within 5days of culture. Whole-cell patch clamp technique was employed to record currents following a 3-min perfusion and stabilization period with TYHX. TYHX administration demonstrated improvements in the ignition phase of impaired SANCs. The half-maximal effective dose of TYHX, as determined by SANC beating frequency, was found to be 323.63μg/mL. Inward current density of I NCX increased in response to TYHX (200 and 400μg/mL), while TYHX enhanced I CaL current density in H/R SANCs, with 400μg/mL exhibiting greater efficacy. Additionally, TYHX regulated the gating mechanisms of I CaL by right-shifting the steady-state inactivation curve and accelerating recovery from inactivation. Notably, TYHX increased the activation time constant under 200 and 400μg/mL, prolonged the fast inactivation time constant τ1 with 400μg/mL, and extended the slow inactivation time constant τ2 with 100 and 400μg/mL. The findings suggest that TYHX may hold promise as a therapeutic intervention for sinus node dysfunction, offering potential avenues for drug development aimed at safeguarding SAN function.