Cardioprotection afforded by chronic exercise is mediated by the sarcolemmal, and not the mitochondrial, isoform of the KATP channel in the rat

被引:99
作者
Brown, DA
Chicco, AJ
Jew, KN
Johnson, MS
Lynch, JM
Watson, PA
Moore, RL [1 ]
机构
[1] Univ Colorado, Cardiovasc Inst, Dept Integrat Physiol, Boulder, CO 80309 USA
[2] Univ Colorado, Dept Med, Div Endocrinol, Denver, CO 80112 USA
[3] Denver Hlth Sci Ctr, Denver, CO 80112 USA
[4] Denver VA Med Ctr, Denver, CO 80112 USA
来源
JOURNAL OF PHYSIOLOGY-LONDON | 2005年 / 569卷 / 03期
关键词
D O I
10.1113/jphysiol.2005.095729
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
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收藏
页码:913 / 924
页数:12
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共 71 条
[11]   Exercise training preserves coronary flow and reduces infarct size after ischemia-reperfusion in rat heart [J].
Brown, DA ;
Jew, KN ;
Sparagna, GC ;
Musch, TI ;
Moore, RL .
JOURNAL OF APPLIED PHYSIOLOGY, 2003, 95 (06) :2510-2518
[12]   Hypoxia-induced preconditioning in adult stimulated cardiomyocytes is mediated by the opening and trafficking of sarcolemmal KATP channels [J].
Budas, GR ;
Jovanovic, S ;
Crawford, RM ;
Jovanovic, A .
FASEB JOURNAL, 2004, 18 (06) :1046-+
[13]   Adenylate kinase phosphotransfer communicates cellular energetic signals to ATP-sensitive potassium channels [J].
Carrasco, AJ ;
Dzeja, PP ;
Alekseev, AE ;
Pucar, D ;
Zingman, LV ;
Abraham, MR ;
Hodgson, D ;
Bienengraeber, M ;
Puceat, M ;
Janssen, E ;
Wieringa, B ;
Terzic, A .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (13) :7623-7628
[14]   Roles of KATP channels in delayed cardioprotection and intracellular Ca2+ in the rat heart as revealed by κ-opioid receptor stimulation with U50,488H [J].
Chen, M ;
Zhou, JJ ;
Kam, KWL ;
Qi, JS ;
Yan, WY ;
Wu, S ;
Wong, TM .
BRITISH JOURNAL OF PHARMACOLOGY, 2003, 140 (04) :750-758
[15]   CONSCIOUS RABBITS BECOME TOLERANT TO MULTIPLE EPISODES OF ISCHEMIC PRECONDITIONING [J].
COHEN, MV ;
YANG, XM ;
DOWNEY, JM .
CIRCULATION RESEARCH, 1994, 74 (05) :998-1004
[16]   Chronic mild hypoxia protects heart-derived H9c2 cells against acute hypoxia/reoxygenation by regulating expression of the SUR2A subunit of the ATP-sensitive K+ channel [J].
Crawford, RM ;
Jovanovic, S ;
Budas, GR ;
Davies, AM ;
Lad, H ;
Wenger, RH ;
Robertson, KA ;
Roy, DJ ;
Ranki, HJ ;
Jovanovic, A .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (33) :31444-31455
[17]   M-LDH serves as a sarcolemmal KATP channel subunit essential for cell protection against ischemia [J].
Crawford, RM ;
Budas, GR ;
Jovanovic, S ;
Ranki, HJ ;
Wilson, TJ ;
Davies, AM ;
Jovanovic, A .
EMBO JOURNAL, 2002, 21 (15) :3936-3948
[18]   Creatine kinase is physically associated with the cardiac ATP-sensitive k+ channel in vivo [J].
Crawford, RM ;
Ranki, HJ ;
Botting, CH ;
Budas, GR ;
Jovanovic, A .
FASEB JOURNAL, 2001, 15 (13) :102-+
[19]   B-type natriuretic peptide limits infarct size in rat isolated hearts via KATP channel opening [J].
D'Souza, SP ;
Yellon, DM ;
Martin, C ;
Schulz, R ;
Heusch, G ;
Onody, A ;
Ferdinandy, P ;
Baxter, GF .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2003, 284 (05) :H1592-H1600
[20]   Phosphotransfer reactions in the regulation of ATP-sensitive K+ channels [J].
Dzeja, PP ;
Terzic, A .
FASEB JOURNAL, 1998, 12 (07) :523-529