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Updated: Jun 15, 2025

Isolation and Kv Channel Recordings in Murine Atrial and Ventricular Cardiomyocytes
Published on: March 12, 2013
Tyrosine phosphorylation of Kir6.2 subunit negatively regulates cardiac KATP channel activity
Yating Zhi1, Bin Yang2, Jianyi Huo1
1Department of Cardiology, The Fourth Affiliated Hospital of Soochow University, Cyrus Tang Medical Institute, Medical College of Soochow University, Suzhou, 215028, China.
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.
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