AUTHOR=Wu Qiaomin , Chang Xing , Wang Yanli , Liu Jinfeng , Guan Xuanke , Liu Zhiming , Liu Ruxiu 

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

JOURNAL=Frontiers in Physiology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2024.1402478

DOI=10.3389/fphys.2024.1402478

ISSN=1664-042X

ABSTRACT=<sec><title>Introduction</title><p>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 (<italic>I</italic><sub>NCX</sub>) and L-type calcium channel (<italic>I</italic><sub>CaL</sub>) of the SAN.</p></sec><sec><title>Methods</title><p>Sinoatrial node cells (SANCs) were isolated and cultured from neonatal Japanese big-eared white rabbits within 24 h of birth. The study encompassed five groups: Control, H/R (hypoxia/reoxygenation), H/R+100 μg/mL TYHX, H/R+200 μg/mL TYHX, and H/R+400 μg/mL TYHX. The H/R model, simulating hypoxia/reoxygenation stress, was induced within 5 days of culture. Whole-cell patch clamp technique was employed to record currents following a 3-min perfusion and stabilization period with TYHX.</p></sec><sec><title>Results</title><p>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 323.63 μg/mL. Inward current density of <italic>I</italic><sub>NCX</sub> increased in response to TYHX (200 and 400 μg/mL), while TYHX enhanced <italic>I</italic><sub>CaL</sub> current density in H/R SANCs, with 400 μg/mL exhibiting greater efficacy. Additionally, TYHX regulated the gating mechanisms of <italic>I</italic><sub>CaL</sub> by right-shifting the steady-state inactivation curve and accelerating recovery from inactivation. Notably, TYHX increased the activation time constant under 200 and 400 μg/mL, prolonged the fast inactivation time constant τ1 with 400 μg/mL, and extended the slow inactivation time constant τ2 with 100 and 400 μg/mL.</p></sec><sec><title>Discussion and conclusion</title><p>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.</p></sec>