Yating Zhi, Bin Yang, Jianyi Huo, Haojie Wang, Bo Yang, Ya-Feng Zhou, Fei Xiao, Hua-Qian Yang
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引用次数: 0
Abstract
The plasma membrane ATP-sensitive potassium (KATP) channel in cardiac myocytes plays a critical role in protecting the heart against ischemic injury. Post-translational modifications regulate KATP channel activity and play a role in cardioprotection. However, the role of tyrosine phosphorylation in KATP channel regulation remains unclear. In this study, we investigated the cardiac KATP channel subtype Kir6.2/SUR2A and demonstrated that a protein tyrosine kinase inhibitor significantly increased the current amplitude through blunting the ATP sensitivity of KATP channels without altering the single-channel current or the channel surface expression. Mutation screening identified Y258 in the Kir6.2 subunit as the tyrosine phosphorylation site of the KATP channel. In cardiomyocytes, KATP channel currents can be reversibly enhanced or weakened by inhibiting the tyrosine kinase epidermal growth factor receptor or the protein tyrosine phosphatase 1B. Furthermore, in a perfused mouse heart model, the inhibitor of epidermal growth factor receptor exhibited a significant cardioprotective effect in a KATP channel dependent manner, indicating the pharmacological potential for treatment of ischemic heart disease.
期刊介绍:
Basic Research in Cardiology is an international journal for cardiovascular research. It provides a forum for original and review articles related to experimental cardiology that meet its stringent scientific standards.
Basic Research in Cardiology regularly receives articles from the fields of
- Molecular and Cellular Biology
- Biochemistry
- Biophysics
- Pharmacology
- Physiology and Pathology
- Clinical Cardiology