Background/Aims The gastrointestinal symptom of diabetes mellitus, chronic constipation, seriously affects patients' life. Whereas, the mechanism of chronic constipation is still ambiguous, resulting in a lack of effective therapies for this symptom. As a part of the smooth muscle cells, interstitial cells of Cajal, and platelet-derived growth factor receptor alpha-positive (PDGFRα+) cells syncytium (SIP syncytium), PDGFRα+ cells play an important role in regulating colonic motility. According to our previous study, in PDGFRα+ cells in colons of diabetic mice, the function of the P2Y1 purinergic receptor/type 3 small-conductance calcium-activated potassium (SK3) channel signaling pathway is strengthened, which may lead to colonic dysmotility. The purpose of this study is to investigate the changes in SK3 channel properties of PDGFRα+ cells in diabetic mice. Methods Whole-cell patch clamp, Western blotting, superoxide dismutase activity measurement, and malondialdehyde measurement were main methods in the present study. Results The present study revealed that when dialysed with low calcium ion (Ca2+) solution, the SK3 current density was significantly decreased in PDGFRα+ cells from diabetic mice. However, the SK3 current density in PDGFRα+ cells was enhanced from diabetic mice when dialysed with high Ca2+ solution. Moreover, hydrogen peroxide-treatment mimicked this phenomenon in SK3 transgenic HEK293 cells. The subunit of SK3 channels, protein kinase CK2, was up-regulated in colonic muscle layers and hydrogen peroxide-treated HEK293 cells. Additionally, protein phosphatase 2A, the subunit of SK3 channels, was not changed in streptozotocin-treated mouse colons or hydrogen peroxide-treated HEK293 cells. Conclusion The diabetic oxidative stress-induced upregulation of CK2 contributed to modulating SK3 channel sensitivity to Ca2+ in colonic PDGFRα+ cells, which may result in colonic dysmotility in diabetic mice.

中文翻译：

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蛋白激酶 CK2 调节来自链脲佐菌素诱导的糖尿病小鼠的结肠血小板衍生生长因子受体 α 阳性细胞中 3 型小电导钙激活钾通道的钙敏感性。

背景/目的糖尿病的消化道症状，慢性便秘，严重影响患者的生活。然而，慢性便秘的机制仍不明确，导致缺乏针对该症状的有效疗法。作为平滑肌细胞、卡哈尔间质细胞和血小板衍生生长因子受体α阳性（PDGFRα+）细胞合胞体（SIP syncytium）的一部分，PDGFRα+细胞在调节结肠运动中起重要作用。根据我们之前的研究，在糖尿病小鼠结肠的 PDGFRα+ 细胞中，P2Y1 嘌呤能受体/3 型小电导钙激活钾 (SK3) 通道信号通路的功能增强，这可能导致结肠运动障碍。本研究的目的是研究糖尿病小鼠 PDGFRα+ 细胞 SK3 通道特性的变化。方法全细胞膜片钳、Western blotting、超氧化物歧化酶活性测定和丙二醛测定是本研究的主要方法。结果 本研究表明，当用低钙离子 (Ca2+) 溶液透析时，糖尿病小鼠 PDGFRα+ 细胞中的 SK3 电流密度显着降低。然而，当用高 Ca2+ 溶液透析时，糖尿病小鼠的 PDGFRα+ 细胞中的 SK3 电流密度增强。此外，过氧化氢处理在 SK3 转基因 HEK293 细胞中模拟了这种现象。SK3 通道的亚基蛋白激酶 CK2 在结肠肌层和过氧化氢处理的 HEK293 细胞中上调。此外，蛋白磷酸酶 2A，SK3 通道的亚基在链脲佐菌素处理的小鼠结肠或过氧化氢处理的 HEK293 细胞中没有改变。结论 糖尿病氧化应激诱导的 CK2 上调有助于调节 SK3 通道对结肠 PDGFRα+ 细胞中 Ca2+ 的敏感性，这可能导致糖尿病小鼠结肠运动障碍。