Department of Physiology, College of Medicine, Gachon University, Lee Gil Ya Cancer and Diabetes Institute, 155 Getbeolro, Yeonsu-gu, Incheon, 21999, South Korea.
Department of Otorhinolaryngology-Head and Neck Surgery, Inha University College of Medicine, 27 Inhang-ro, Jung-gu, Incheon, 22332, South Korea.
Cell Tissue Res. 2021 Mar;383(3):1017-1024. doi: 10.1007/s00441-020-03299-2. Epub 2020 Nov 7.
Although cardiac tissue is considered a target of gravitational force (g-force), the mechanism of hypergravity on the ion modulation or identification of ion transporters is still unknown. Thus, we determine the effect of hypergravity on a physical force-sensitive cytokine, IL-6 and its related channel activity to investigate rat cardiac function changes in response to accelerated g-force. Serum IL-6 levels and intracellular calcium levels of the right atrium were moderately increased under hypergravity stimulation (4g). IL-6 was involved in the modulation of sodium-potassium-chloride cotransporter (Nkcc) activity. Surprisingly, the right atrium under 4g revealed significantly enhanced Nkcc1 activity. The use of IL-6 on the NKCC1-overexpressed or native NKCC-expressing cells also showed enhanced NKCC1 activity. Hypergravity conditions were also involved in the oxidative stress activated Trpm2 channel and revealed an enhanced expression of the Trpm2 channel under 4g in the rat right atrium. In conclusion, hypergravity revealed that moderate increases in serum IL-6 and enhanced Nkcc1 activity was modulated by IL-6. In addition, enhanced Trpm2 channel expression could be involved in the increased intracellular calcium levels of the right atrium under hypergravitational force. We therefore address that enhanced physical force-sensitive cytokine and oxidative stress by the gravitational force mediate activation of the cotransporter involved in possibilities of edema and calcium loading in cardiac tissue.
尽管心肌组织被认为是重力（g-force）的靶点，但超重力对离子调制或离子转运体识别的机制尚不清楚。因此，我们确定超重力对物理力敏感细胞因子 IL-6 及其相关通道活性的影响，以研究大鼠心脏对加速 g-force 的反应功能变化。在超重力刺激（4g）下，血清 IL-6 水平和右心房细胞内钙离子水平适度增加。IL-6 参与了钠钾氯共转运体（Nkcc）活性的调节。令人惊讶的是，4g 下的右心房显示出明显增强的 Nkcc1 活性。在 NKCC1 过表达或天然 NKCC 表达细胞上使用 IL-6 也显示出增强的 NKCC1 活性。超重力条件还涉及氧化应激激活的 Trpm2 通道，并且在大鼠右心房中，4g 下 Trpm2 通道的表达增强。总之，超重力表明血清 IL-6 的适度增加和 Nkcc1 活性的增强是由 IL-6 调节的。此外，增强的 Trpm2 通道表达可能涉及超重力下右心房细胞内钙离子水平的增加。因此，我们认为增强的物理力敏感细胞因子和由重力介导的氧化应激激活了共转运体，这可能导致心肌组织水肿和钙超载。
