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

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 ³¹P 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. Received: 2 December 2002, Returned for revision: 9 January 2003, Revision received: 26 March 2003, Accepted: 8 April 2003, Published online: 9 May 2003 RID="*" ID="*"Publishers Note In the “online-first” publication of this article figure 3 and 4 were erroneously swapped. This mistake was corrected in the printed version and in the final online version on the authors request. The publisher apologizes for this oversight. Correspondence to: I. Hassinen