Qin Lu, Zhang Xuexin, Li Jianhua
Heart and Vascular Institute, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA.
Physiol Rep. 2025 Jul;13(13):e70457. doi: 10.14814/phy2.70457.
We examined if the hindlimb muscle ischemia-reperfusion (IR) alters ASIC3-mediated muscle afferent activity in regulating the exercise pressor reflex (EPR). APETx2 (an ASIC3 antagonist) was arterially injected into the hindlimb before static muscle contraction. The mean arterial pressure (MAP) and heart rate (HR) were recorded. ASIC3-mediated MAP response was studied via intra-arterially injected lactic acid (LA). Western blot and immunofluorescence were used to determine the ASIC3 expression and location in L4-6 dorsal root ganglion (DRG). Calcium imaging was applied to detect pH6.7-induced Ca entry in the isolated muscle DRG neurons. IR amplified the peak MAP response to muscle contraction (sham vs. IR: p = 0.031), which was reduced by the blockage of ASIC3 with APETx2 (baseline vs. blockage: p < 0.001). The peak MAP responses to LA were increased in IR rats (sham vs. IR, 1 μmol/kg: p < 0.05; 2 and 4 μmol/kg: sham vs. IR, p < 0.01) and were reduced by APETx2 (baseline LA control vs. blockage: p = 0.013). ASIC3 protein expression was increased in IR L4-6 DRGs (sham vs. IR, p = 0.012). APETx2 attenuated the pH 6.7-induced Ca entry (ΔF340/F380: sham vs. IR, p = 0.017; IR vs. IR + APETx2, p = 0.003). Increased ASIC3 signaling amplifies muscle afferent activity and exacerbates the EPR following IR.
我们研究了后肢肌肉缺血再灌注（IR）是否会改变酸敏感离子通道3（ASIC3）介导的肌肉传入活动对运动加压反射（EPR）的调节。在静态肌肉收缩前，将APETx2（一种ASIC3拮抗剂）动脉内注射到后肢。记录平均动脉压（MAP）和心率（HR）。通过动脉内注射乳酸（LA）研究ASIC3介导的MAP反应。采用蛋白质免疫印迹法和免疫荧光法确定ASIC3在L4 - 6背根神经节（DRG）中的表达和定位。应用钙成像检测pH6.7诱导的分离肌肉DRG神经元中的钙内流。IR增强了对肌肉收缩的MAP峰值反应（假手术组与IR组：p = 0.031），而用APETx2阻断ASIC3可降低该反应（基线组与阻断组：p < 0.001）。IR大鼠对LA的MAP峰值反应增加（假手术组与IR组，1 μmol/kg：p < 0.05；2和4 μmol/kg：假手术组与IR组，p < 0.01），且被APETx2降低（基线LA对照组与阻断组：p = 0.013）。IR的L4 - 6 DRG中ASIC3蛋白表达增加（假手术组与IR组，p = 0.012）。APETx2减弱了pH 6.7诱导的钙内流（ΔF340/F380：假手术组与IR组，p = 0.017；IR组与IR + APETx2组，p = 0.003）。ASIC3信号增强会放大肌肉传入活动，并在IR后加剧EPR。
