Infection with AV-SUR2A protects H9C2 cells against metabolic stress: a mechanism of SUR2A-mediated cytoprotection independent from the K(ATP) channel activity.
Transgenic mice overexpressing SUR2A, a subunit of ATP-sensitive K(+) (K(ATP)) channels, acquire resistance to myocardial ischaemia. However, the mechanism of SUR2A-mediated cytoprotection is yet to be fully understood. Adenoviral SUR2A construct (AV-SUR2A) increased SUR2A expression, number of K(ATP) channels and subsarcolemmal ATP in glycolysis-sensitive manner in H9C2 cells. It also increased K(+) current in response to chemical hypoxia, partially preserved subsarcolemmal ATP and increased cell survival. Kir6.2AFA, a mutant form of Kir6.2 with largely decreased K(+) conductance, abolished the effect of SUR2A on K(+) current, did not affect SUR2A-induced increase in subsarcolemmal ATP and partially inhibited SUR2A-mediated cytoprotection. Infection with 193gly-M-LDH, an inactive mutant of muscle lactate dehydrogenase, abolished the effect of SUR2A on K(+) current, subsarcolemmal ATP and cell survival; the effect of 193gly-M-LDH on cell survival was significantly more pronounced than those of Kir6.2AFA. We conclude that AV-SUR2A increases resistance to metabolic stress in H9C2 cells by increasing the number of sarcolemmal K(ATP) channels and subsarcolemmal ATP.
Du
Qingyou
Q
Division of Medical Sciences, Centre for Cardiovascular and Lung Biology, Ninewells Hospital and Medical School, University of Dundee, UK.
Jovanović
Sofija
S
Sukhodub
Andriy
A
Jovanović
Aleksandar
A
D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D054086:KATP Channels / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011955:Receptors, Drug / Q000235:genetics / Q000378:metabolism; D012508:Sarcolemma / Q000378:metabolism; D013312:Stress, Physiological / Q000502:physiology*; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel
D018528:ATP-Binding Cassette Transporters; D000255:Adenosine Triphosphate; D054086:KATP Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel; C577511:Abcc9 protein, mouse