| First Author | Song NN | Year | 2023 |
| Journal | J Neurogastroenterol Motil | Volume | 29 |
| Issue | 2 | Pages | 250-261 |
| PubMed ID | 37019869 | Mgi Jnum | J:354087 |
| Mgi Id | MGI:7719086 | Doi | 10.5056/jnm22052 |
| Citation | Song NN, et al. (2023) Protein Kinase CK2 Modulates the Calcium Sensitivity of Type 3 Small-conductance Calcium-activated Potassium Channels in Colonic Platelet-derived Growth Factor Receptor Alpha-positive Cells From Streptozotocin-induced Diabetic Mice. J Neurogastroenterol Motil 29(2):250-261 |
| abstractText | 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 (PDGFRalpha(+)) cells syncytium (SIP syncytium), PDGFRalpha(+) cells play an important role in regulating colonic motility. According to our previous study, in PDGFRalpha(+) 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 PDGFRalpha(+) 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 (Ca(2+)) solution, the SK3 current density was significantly decreased in PDGFRalpha(+) cells from diabetic mice. However, the SK3 current density in PDGFRalpha(+) cells was enhanced from diabetic mice when dialysed with high Ca(2+) 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 Ca(2+) in colonic PDGFRalpha(+) cells, which may result in colonic dysmotility in diabetic mice. |
