Cardioprotection afforded by chronic exercise is mediated by the sarcolemmal, and not the mitochondrial, isoform of the KATP channel in the rat
Cardioprotection afforded by chronic exercise is mediated by the sarcolemmal, and not the mitochondrial, isoform of the KATP channel in the rat
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DOI：
10.1113/jphysiol.2005.095729
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发表时间：
2005-12-15
影响因子：
5.5
通讯作者：
Moore, RL
中科院分区：
文献类型：
--
作者：
Brown, DA;Chicco, AJ;Moore, RL
本研究旨在探讨心肌ATP敏感性钾(K-ATP)通道在运动性脑缺血再灌注(I-R)损伤保护中的作用。雌性大鼠要么久坐(SED)，要么运动12周(Tr)。切除心脏，接受1-2小时的局部I-R程序。在缺血前，用HMR 1098(SedHMR和TrHMR)阻断心肌细胞膜K-ATP通道，用5-羟基癸酸阻断线粒体(5HD；Sed5HD和Tr5HD)，或用不含药物的缓冲液灌流(SED和Tr)。Tr动物的心肌梗死面积明显较小(Tr和SED风险区域的35.4+/-2.3和44.7+/-3.0%)。线粒体K-ATP阻断剂不能消除训练诱导的心肌梗死面积缩小(Tr5HD和Sed5HD分别为30.0+/-3.4和38.0+/-2.6)，但肌膜K-ATP阻断剂可完全消除训练诱导的心肌保护作用。梗塞面积分别为TrHMR和SED HMR危险区的71.2+/-3.3和64.0+/-2.4%。肌膜K-ATP通道在Tr诱导的保护中的作用也被训练后肌膜K-ATP通道两个亚单位的显著增加所支持。在Tr动物的心脏中，LV发展压保存较好，且不受HMR 1098的影响。5HD减少了压力发展，无论训练状态如何，从15min的缺血到整个方案的持续时间。这种机械功能障碍可能是由于5HD诱导的缺血再灌注后心肌细胞内钙含量的增加所致。本研究的主要发现是：(1)与所有其他已知的延迟心肌保护形式不同，慢性运动后的心肌保护不会被5HD取消；(2)药物阻断肌膜K-ATP通道可抵消运动对心脏的保护作用；(3)慢性训练后肌膜K-ATP通道的表达增加。
This study was conducted to examine the role of myocardial ATP-sensitive potassium (K-ATP) channels in exercise-induced protection from ischaemia-reperfusion (I-R) injury. Female rats were either sedentary (Sed) or exercised for 12 weeks (Tr). Hearts were excised and underwent a 1-2 h regional I-R protocol. Prior to ischaemia, hearts were subjected to pharmacological blockade of the sarcolemmal K-ATP channel with HMR 1098 (SedHMR and TrHMR), mitochondrial blockade with 5-hydroxydecanoic acid (5HD; Sed5HD and Tr5HD), or perfused with buffer containing no drug (Sed and Tr). Infarct size was significantly smaller in hearts from Tr animals (35.4 +/- 2.3 versus 44.7 +/- 3.0% of the zone at risk for Tr and Sed, respectively). Mitochondrial K-ATP blockade did not abolish the training-induced infarct size reduction (30.0 +/- 3.4 versus 38.0 +/- 2.6 in Tr5HD and Sed5HD, respectively); however, sarcolemmal K-ATP blockade completely eradicated the training-induced cardioprotection. Infarct size was 71.2 +/- 3.3 and 64.0 +/- 2.4% of the zone at risk for TrHMR and Sed HMR. The role of sarcolemmal K-ATP channels in Tr-induced protection was also supported by significant increases in both subunits of the sarcolemmal K-ATP channel following training. LV developed pressure was better preserved in hearts from Tr animals, and was not influenced by addition of HMR 1098. 5HD decreased pressure development regardless of training status, from 15 min of ischaemia through the duration of the protocol. This mechanical dysfunction was likely to be due to a 5HD-induced increase in myocardial Ca2+ content following I-R. The major findings of the present study are: (1) unlike all other known forms of delayed cardioprotection, infarct sparing following chronic exercise was not abolished by 5HD; (2) pharmacological blockade of the sarcolemmal K-ATP channel nullified the cardioprotective benefits of exercise training; and (3) increased expression of sarcolemmal K-ATP channels was observed following chronic training.