Tongyang Huoxue decoction (TYHX) ameliorating hypoxia/reoxygenation-induced disequilibrium of calcium homeostasis via regulating β-tubulin in rabbit sinoatrial node cells

Zhang, Xinai; Zhou, Yutong; Chang, Xing; Wu, Qiaomin; Liu, Zhiming; Liu, Rongda

doi:10.1016/j.jep.2023.117006

Cited by 1 publication

(1 citation statement)

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“…Pathological damage such as hypoxia and inflammation can induce fibrosis of the sinoatrial node tissue ( Zhang et al, 2020 ), which could also reduce I CaL by 50%. Previous studies have observed that hypoxia/reoxygenation injury leads to a decrease in Cav1.3 expression in SANCs and that TYHX protects damaged SANCs and restores Cav1.3 expression ( Zhang et al, 2024 ). In this study, we also found that hypoxia/reoxygenation injury decreased I CaL amplitude and density in SANCs, while TYHX increased current density and restored the I-V curve of I CaL in damaged SANCs, partially reversing the I CaL changes caused by hypoxia/reoxygenation injury.…”

Section: Discussionmentioning

confidence: 98%

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

Wu,

Chang,

Wang

et al. 2024

Front. Physiol.

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IntroductionThis 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 (INCX) and L-type calcium channel (ICaL) of the SAN.MethodsSinoatrial 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.ResultsTYHX 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 INCX increased in response to TYHX (200 and 400 μg/mL), while TYHX enhanced ICaL current density in H/R SANCs, with 400 μg/mL exhibiting greater efficacy. Additionally, TYHX regulated the gating mechanisms of ICaL 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.Discussion and conclusionThe 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.

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Section: Discussionmentioning

confidence: 98%