Accumulation of intramyocyte TRPV1-mediated calcium during heat stress is inhibited by concomitant muscle contractions
Accumulation of intramyocyte TRPV1-mediated calcium during heat stress is inhibited by concomitant muscle contractions
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DOI：
10.1152/japplphysiol.00668.2018
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发表时间：
2019-03-01
影响因子：
3.3
通讯作者：
Kano, Yutaka
中科院分区：
文献类型：
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作者：
Ikegami, Ryo;Eshhna, Hiroaki;Kano, Yutaka
热应激通过瞬时受体电位香草酸 1 (TRPV1) 通道促进肌细胞内钙浓度 ([Ca2+](i)) 积累。我们测试了这样的假设：伴随热应激的肌肉收缩活动会通过 TRPV1 加速 [Ca2+](i) 的增加，进一步损害 [Ca2+](i) 稳态。将成年 Wistar 大鼠的斜方肌在体内取出并装载荧光 Ca2+ 探针 fura 2-AM。使用热应激（肌肉表面温度40℃）作为TRPV1激活剂。伴随着热应力，电诱导等长收缩（100 Hz，5-10 V，30 s）。使用体内荧光显微镜测定 [Ca2+](i) 20 分钟，并通过蛋白质印迹测定 TRPV1 的磷酸化反应。热应激导致 20 分钟时 [Ca2+](i) 显着增加 18.5 +/- 8.1%，TRPV1 磷酸化 (+231%)，添加 TRPV1 抑制剂（辣椒西平）可抑制这种磷酸化。然而，与预期相反，热应激和等长收缩条件几乎完全抑制了 TRPV1 磷酸化和随之而来的 [Ca2+](i) 升高 (0.05)。总之，这种体内生理模型证明，等长肌肉收缩可以抑制 TRPV1 的磷酸化反应，并在热应激期间维持 [Ca2+](i) 稳态。新的和值得注意的这项研究是第一篇关于骨骼肌纤维肌浆中肌细胞内钙浓度 ([Ca2+](i)) 动态增加的文献，以响应热应激，同时保留肌肉血流。 40 摄氏度的热应激会驱动肌质 [Ca2+](i) 积累，并与瞬时受体电位香草酸 1 (TRPV1) 磷酸化相一致。然而，肌肉收缩通过 TRPV1 去磷酸化导致 TRPV1 通道失活。即使在高肌肉温度下，TRPV1 通过等长收缩失活也能维持 [Ca2+](i) 稳态。
Heat stress promotes intramyocyte calcium concentration ([Ca2+](i)) accumulation via transient receptor potential vanilloid 1 (TRPV1) channels. We tested the hypothesis that muscle contractile activity concomitant with heat stress would accelerate the increase in [Ca2+](i) via TRPV1, further impairing [Ca2+](i) homeostasis. Spinotrapezius muscles of adult Wistar rats were exteriorized in vivo and loaded with the fluorescent Ca2+ probe fura 2-AM. Heat stress (muscle surface temperature 40 degrees C) was used as TRPV1 activator. An isometric contraction (100 Hz, 5-10 V, 30 s) was induced electrically concomitant with heat stress. [Ca2+](i) was determined for 20 min using in vivo fluorescence microscopy, and the phosphorylation response of TRPV1 was determined by Western blotting. Heat stress induced a significant [Ca2+](i) increase of 18.5 +/- 8.1% at 20 min and TRPV1 phosphorylation (+231%), which was inhibited by addition of the TRPV1 inhibitor (capsazepine). However, contrary to expectations, the heat stress and isometric contraction condition almost completely inhibited TRPV1 phosphorylation and the consequent [Ca2+](i) elevation ( 0.05). In conclusion, this in vivo physiological model demonstrated that isometric muscle contraction(s) can suppress the phosphorylation response of TRPV1 and maintain [Ca2+](i) homeostasis during heat stress.NEW & NOTEWORTHY This investigation is the first document the dynamics of intramyocyte calcium concentration ([Ca2+](i)) increase in the myoplasm of skeletal muscle fibers in response to heat stress where the muscle blood flow is preserved. Heat stress at 40 degrees C drives a myoplasmic [Ca2+](i) accumulation in concert with transient receptor potential vanilloid 1 (TRPV1) phosphorylation. However, muscle contraction caused TRPV1 channel deactivation by dephosphorylation of TRPV1. TRPV1 inactivation via isometric contraction(s) permits maintenance of [Ca2+](i) homeostasis even under high imposed muscle temperature.