Habib Mahdi1, Aleksandar Jovanović2,3. 1. Department of Basic and Clinical Sciences, University of Nicosia Medical School, 21 Ilia Papakyriakou Engomi, P.O. Box 24005, 2414, CY-1700, Nicosia, Cyprus. 2. Department of Basic and Clinical Sciences, University of Nicosia Medical School, 21 Ilia Papakyriakou Engomi, P.O. Box 24005, 2414, CY-1700, Nicosia, Cyprus. jovanovic.a@unic.ac.cy. 3. Center for Neuroscience and Integrative Brain Research (CENIBRE), University of Nicosia Medical School, Nicosia, Cyprus. jovanovic.a@unic.ac.cy.
Abstract
BACKGROUND: ATP-sensitive K+ (KATP) channels link the metabolic state of the cell with membrane excitability and SUR2A serves as a regulatory subunit of sarcolemmal KATP 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 KATP channels in the sarcolemma. Increased numbers of sarcolemmal KATP channels protect cardiomyocytes against different types of stress by improving the timing of KATP channels opening, but, also, by catalyzing ATP production in subsarcolemmal space. Fully-assembled sarcolemmal KATP 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.
BACKGROUND: ATP-sensitive K+ (KATP) channels link the metabolic state of the cell with membrane excitability and SUR2A serves as a regulatory subunit of sarcolemmal KATP 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 KATP channels in the sarcolemma. Increased numbers of sarcolemmal KATP channels protect cardiomyocytes against different types of stress by improving the timing of KATP channels opening, but, also, by catalyzing ATP production in subsarcolemmal space. Fully-assembled sarcolemmal KATP 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.
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