Ischaemic preconditioning and a mitochondrial KATP channel opener both produce cardioprotection accompanied by F1F0-ATPase inhibition in early ischaemia

被引:32
作者
Ala-Rämi, A
Ylitalo, KV
Hassinen, IE
机构
[1] Univ Oulu, Dept Med Biochem & Mol Biol, Oulu 90014, Finland
[2] Univ Oulu, Dept Internal Med, Oulu 90014, Finland
关键词
ischaemia; preconditioning; K-ATP channel; ATP synthase diazoxide;
D O I
10.1007/s00395-003-0413-z
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Ischaemic preconditioning gives powerful protection against prolonged ischaemia affecting several intracellular regulatory and messenger pathways, although their mutual importance is far from established. Protective, preconditioning-like effects have been reported for K-ATP channel openers, and most of the evidence points to the mitochondrial K-ATP channels. We show here that the K-ATP channel opener diazoxide, which acts selectively on the mitochondrial channel, causes potentiation of ischaemic inhibition of mitochondrial ATP synthase (F1F0-ATPase) along with cardioprotection. These effects are comparable with that of ischaemic preconditioning. The administration of diazoxide did not affect the cellular energy state as monitored with P-31 NMR. The actions of both diazoxide and ischaemic preconditioning were prevented by 5-hydroxydecanoate, a specific inhibitor of the mitochondrial K-ATP channel. Thus mitochondrial K-ATP channel opening and ischaemic preconditioning must share common mechanisms of action involving mitochondrial F1F0-ATPase, although involvement of the energy state in protection could not be proved.
引用
收藏
页码:250 / 258
页数:9
相关论文
共 47 条
[1]   SAFRANINE AS A PROBE OF MITOCHONDRIAL-MEMBRANE POTENTIAL [J].
AKERMAN, KEO ;
WIKSTROM, MKF .
FEBS LETTERS, 1976, 68 (02) :191-197
[2]  
BERGMEYER HU, 1970, METHODEN ENZYMATISCH, P533
[3]   Modulation of the oligomerization state of the bovine F1-ATPase inhibitor protein, IF1, by pH [J].
Cabezon, E ;
Butler, PJG ;
Runswick, MJ ;
Walker, JE .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (33) :25460-25464
[4]   REGULATION OF THE MITOCHONDRIAL ATP SYNTHASE IN INTACT RAT CARDIOMYOCYTES [J].
DAS, AM ;
HARRIS, DA .
BIOCHEMICAL JOURNAL, 1990, 266 (02) :355-361
[5]   Effects of cromakalim and glibenclamide on myocardial high energy phosphates and intracellular pH during ischemia-reperfusion: P-31 NMR studies [J].
Docherty, JC ;
Gunter, HE ;
Kuzio, B ;
Shoemaker, L ;
Yang, LJ ;
Deslauriers, R .
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 1997, 29 (06) :1665-1673
[6]   Mechanisms by which opening the mitochondrial ATP-sensitive K+ channel protects the ischemic heart [J].
Dos Santos, P ;
Kowaltowski, AJ ;
Laclau, MN ;
Seetharaman, S ;
Paucek, P ;
Boudina, S ;
Thambo, JB ;
Tariosse, L ;
Garlid, KD .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2002, 283 (01) :H284-H295
[7]   Do mitochondrial KATP channels serve as triggers rather than end-effectors of ischemic preconditioning's protection? [J].
Downey, JM ;
Cohen, MV .
BASIC RESEARCH IN CARDIOLOGY, 2000, 95 (04) :272-274
[8]   Ischemic preconditioning in rats:: role of mitochondrial KATP channel in preservation of mitochondrial function [J].
Fryer, RM ;
Eells, JT ;
Hsu, AK ;
Henry, MM ;
Gross, GJ .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2000, 278 (01) :H305-H312
[9]   Opening mitochondrial KATP in the heart -: what happens, and what does not happen [J].
Garlid, KD .
BASIC RESEARCH IN CARDIOLOGY, 2000, 95 (04) :275-279
[10]  
Garlid KD, 1997, CIRC RES, V81, P1072