Abstract
Muscle form of lactate dehydrogenase (M-LDH), a minor LDH form in cardiomyocytes, physically interacts with ATP-sensitive K+ (K-ATP) channel-forming subunits. Here, we have shown that expression of 193gly-M-LDH, an inactive mutant of M-LDH, inhibit regulation of the K-ATP channels activity by LDH substrates in embryonic rat heart H9C2 cells. In cells expressing 193gly-M-LDH chemical hypoxia has failed to activate K-ATP channels. The similar results were obtained in H9C2 cells expressing Kir6.2AFA, a mutant form of Kir6.2 with largely decreased K+ conductance. Kir6.2AFA has slightly, but significantly, reduced cellular survival under chemical hypoxia while the deleterious effect of 193gly-M-LDH was significantly more pronounced. The levels of total and subsarcolemmal ATP in H9C2 cells were not affected by Kir6.2AFA, but the expression of 193gly-M-LDH led to lower levels of subsarcolemmal ATP during chemical hypoxia. We conclude that M-LDH regulates both the channel activity and the levels of subsarcolemmal ATP and that both mechanism contribute to the M-LDH-mediated cytoprotection. (C) 2009 Elsevier B.V. All rights reserved.
Original language | English |
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Pages (from-to) | 1379-1386 |
Number of pages | 8 |
Journal | Biochimica et Biophysica Acta (BBA) - Molecular Cell Research |
Volume | 1793 |
Issue number | 8 |
DOIs | |
Publication status | Published - Aug 2009 |
Keywords
- Lactate dehydrogenase
- K-ATP channel
- H9C2 cell
- Hypoxia
- K-ATP CHANNELS
- SENSITIVE POTASSIUM CHANNELS
- PREVENTS MEMBRANE DEPOLARIZATION
- CHEMICAL HYPOXIA-REOXYGENATION
- RABBIT VENTRICULAR MYOCYTES
- METABOLIC STRESS
- GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE
- SKELETAL-MUSCLE
- RAT-HEART
- CARDIOMYOCYTES