Du Qingyou, Jovanović Sofija, Sukhodub Andriy, Jovanović Aleksandar
Division of Medical Sciences, Centre for Cardiovascular and Lung Biology, Ninewells Hospital and Medical School, University of Dundee, UK.
Biochim Biophys Acta. 2010 Mar;1803(3):405-15. doi: 10.1016/j.bbamcr.2010.01.018. Epub 2010 Feb 1.
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.
过表达ATP敏感性钾（K(ATP)）通道亚基SUR2A的转基因小鼠对心肌缺血具有抗性。然而，SUR2A介导的细胞保护机制尚未完全明确。腺病毒SUR2A构建体（AV-SUR2A）以糖酵解敏感的方式增加了H9C2细胞中SUR2A的表达、K(ATP)通道数量和肌膜下ATP。它还增加了对化学性缺氧的钾电流，部分保留了肌膜下ATP并提高了细胞存活率。Kir6.2AFA是Kir6.2的一种突变形式，其钾电导大幅降低，消除了SUR2A对钾电流的影响，不影响SUR2A诱导的肌膜下ATP增加，并部分抑制了SUR2A介导的细胞保护作用。用肌肉乳酸脱氢酶的无活性突变体193gly-M-LDH感染，消除了SUR2A对钾电流、肌膜下ATP和细胞存活的影响；193gly-M-LDH对细胞存活的影响比Kir6.2AFA的影响明显更显著。我们得出结论，AV-SUR2A通过增加肌膜K(ATP)通道数量和肌膜下ATP来提高H9C2细胞对代谢应激的抗性。
