M-LDH physically associated with sarcolemmal K ATP channels mediates cytoprotection in heart embryonic H9C2 cells.

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; 10mM). 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.

• Authors: Sofija Jovanović, Qingyou Du, Andriy Sukhodub, Aleksandar Jovanović
• Journal: The international journal of biochemistry & cell biology (Int J Biochem Cell Biol) Vol. 41 Issue 11 Pg. 2295-301 (Nov 2009) ISSN: 1878-5875 [Electronic] Netherlands
• PMID: 19464385 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• KATP Channels
• Kir6.2 channel
• Potassium Channels, Inwardly Rectifying
• Adenosine Triphosphate
• L-Lactate Dehydrogenase

Topics

• Adenosine Triphosphate (metabolism)
• Animals
• Cell Hypoxia
• Cell Line
• Cell Survival
• Cytoprotection
• Genes, Dominant
• Heart (embryology)
• Intracellular Space (metabolism)
• Ion Channel Gating
• KATP Channels
• L-Lactate Dehydrogenase (metabolism)
• Muscles (enzymology)
• Myocytes, Cardiac (cytology, enzymology)
• Potassium Channels, Inwardly Rectifying (metabolism)
• Protein Binding
• Rats
• Sarcolemma (metabolism)