Abstract
Muscle form of lactate dehydrogenase (M-LDH) physically associate with K-ATP, channel subunits, Kir6.2 and SUR2A, and is an integral part of the ATP-sensitive K+ (K-ATP) channel protein complex in the heart. Here, we have shown that concomitant introduction of viral constructs containing truncated and mutated forms of M-LDH (Delta M-LDH) and 193gly-M-LDH respectively, generate a phenotype of rat heart embryonic H9C2 cells that do not contain functional M-LDH as a part of the K-ATP, channel protein complex. The K+ current was increased in wild type cells, but not in cells expressing Delta M-LDH/193gly-M-LDH. when they were exposed to chemical hypoxia induced by 2,4 dinitrophenol (DNP: 10 mM). At the same time, the outcome of chemical hypoxia was much worse in Delta M-LDH/193gly-M-LDH phenotype than in the control one, and that was associated with increased loss of intracellular ATP in cells infected with Delta M-LDH/193gly-M-LDH. On the other hand, cells expressing Kir6.2AFA. a Kir6.2 mutant that abolishes K-ATP channel conductance without affecting intracellular ATP levels. survived chemical hypoxia much better than cells expressing Delta M-LDH/193gly-M-LDH. Based on the obtained results. we conclude that M-LDH physically associated with Kir6.2/SUR2A regulates the activity of sarcolemmal K-ATP channels as well as an intracellular ATP production during metabolic stress, both of which are important for cell survival. (C) 2009 Elsevier Ltd. All rights reserved.
Original language | English |
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Pages (from-to) | 2295-2301 |
Number of pages | 7 |
Journal | International Journal of Biochemistry & Cell Biology |
Volume | 41 |
Issue number | 11 |
DOIs | |
Publication status | Published - Nov 2009 |
Keywords
- M-LDH
- K-ATP channels
- Chemical hypoxia
- ATP
- H9C2 cells
- PREVENTS MEMBRANE DEPOLARIZATION
- CHEMICAL HYPOXIA-REOXYGENATION
- SENSITIVE POTASSIUM CHANNELS
- GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE
- CARDIOMYOCYTES
- KINASE
- EXPRESSION
- ISCHEMIA
- SUBUNITS
- SERVES