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Title: Ventricular myocyte sarcolemmal Kir6.1/SUR2B potassium channels : a potential effector of cardioprotection
Author: Chen, Shen
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 2018
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KATP channels are ubiquitously expressed and are said to couple cellular metabolic state and electrical excitability. The KATP channel complex is composed of two subunits in a hetero-octameric structure, with Kir6 subunit form the pore and sulphonylurea receptors (SUR) as β-subunits. In the heart, KATP channels are considered to be composed of the Kir6.2/SUR2A combination and play a key role in responding to metabolic stress as well as in cardioprotection. It is hypothesised that opening of the cardiac SarcoKATP channel shortens the action potential duration so reducing the ATP consumption during an ischaemic event to preserve energy and so limit Ca2+ overload. Previous data (unpublished) suggested there was a Kir6.1-like current, with constitutive activity, on the rat cardiomyocyte sarcolemmal membrane. In this study, firstly, the Kir6.1-like channel was formally identified by using electrophysiology patch clamp and specific pharmacological inhibitors. Secondly, further evidence was acquired using specific knockdown the pore-forming and β-subunits using adenoviral-introduced shRNA. Finally, for SarcoKir6.1 current was investigated in control cardiomyocytes and in IPC, adenosine-induced cardioprotection and sex-specific cardioprotection. In this study, a new small-conductance KATP channel was identified at the cardiac sarcolemmal surface along with the large-conductance channel. These findings suggest that there are two components to IKATP in the heart, IKATP-SC, composed of Kir6.1/SUR2B subunits, and IKATP-LC which is the classically thought of cardiac Kir6.2/SURA complex. It is suggested the newly discovered IKATP-SC plays an important role in regulating action potential duration as well as mediating cardioprotection. This IKATP-SC may help explain the role that cardiac sarcolemmal KATP plays in cardioprotection.
Supervisor: Rainbow, Rich ; Davies, Noel ; Lodwick, Dave Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available