Referenced in: none

Automatically associated channels: Kir6.2

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

Authors: Sofija Jovanović, Qingyou Du, Andriy Sukhodub, Aleksandar Jovanović

Journal, date & volume: Int. J. Biochem. Cell Biol., 2009 Nov , 41, 2295-301

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/19464385

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.