SUR2A as a base for cardioprotective therapeutic strategies

Abstract

Background: ATP-sensitive K⁺ (K_ATP) channels link the metabolic state of the cell with membrane excitability and SUR2A serves as a regulatory subunit of sarcolemmal K_ATP channels. The aim of the present study was to review SUR2A-mediated cardioprotection.

Methods and results: A related literature search in PubMed, Scopus, Web of Science, Google Scholar, and Science direct was performed. Levels of SUR2A regulate number of fully assembled K_ATP channels in the sarcolemma. Increased numbers of sarcolemmal K_ATP channels protect cardiomyocytes against different types of stress by improving the timing of K_ATP channels opening, but, also, by catalyzing ATP production in subsarcolemmal space. Fully-assembled sarcolemmal K_ATP channels protein complex contain ATP-producing enzymes in addition to channel subunits, SUR2A and Kir6.2. An increase in the number of fully-assembled channels results in increased levels of ATP-producing enzymes and subsarcolemmal ATP, which is beneficial in ischemia. Expression of SUR2A is regulated by diverse mechanisms, including AMPK, PI3K/Akt, and ERK1/2 as well as intracellular levels of NAD+/NADH and ATP. There are many compounds and treatments that can be used to regulate SUR2A and some of them seem to be clinically viable options. The most suitable medication to use to increase SUR2A and confer cardioprotection in the clinical setting seems to be nicotinamide. It is one of the safest compounds used in clinical practice and all pre-clinical studies demonstrated that it is an efficient cardioprotective agent.

Conclusions: Taken all together, SUR2A-based cardioprotection is a likely efficient and safe cardioprotective strategy that can be quickly introduced into clinical practice.

Keywords: Cardioprotection; Ischemic heart disease; SUR2A.