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(Circulation Research. 2001;88:750.)
© 2001 American Heart Association, Inc.

Editorials

Opening of Mitochondrial K_ATP Channels Triggers Cardioprotection

Are Reactive Oxygen Species Involved?

Yongge Liu, Brian O’Rourke

From the Maryland Research Laboratories (Y.L.), Otsuka Maryland Research Institute, Rockville, Md, and Institute of Molecular Cardiobiology (B.O’R.), Johns Hopkins University, Baltimore, Md.

Correspondence to Yongge Liu, PhD, Maryland Research Laboratories, Otsuka Maryland Research Institute, 9900 Medical Center Dr, Rockville, MD 20850. E-mail yonggel@otsuka.com

Key Words: preconditioning • diazoxide • K_ATP channel • mitochondria • reactive oxygen species

	Introduction

 
Ischemic preconditioning, a phenomenon in which brief episodes of ischemia and reperfusion paradoxically protect the heart against subsequent lethal ischemia,¹ has been conceptually divided into triggers and mediators/effectors.^{2 3} The trigger, which acts before the index ischemia, is followed by the protection of mediators/effectors during the lethal ischemia. Known triggers include activation of adenosine receptors, ₁-adrenegic receptors and opioid receptors, elevated intracellular Ca²⁺, and increased reactive oxygen species (ROS).² The mitochondrial ATP-dependent potassium channel (mitoK_ATP) has been proposed to be the mediator of this protection.⁴ The link between the trigger and effector may be the activation of protein kinases (eg, protein kinase C, tyrosine kinase, and downstream kinases), which may phosphorylate mitoK_ATP, causing the channel to open early and/or to a greater extent to reduce injury during the lethal ischemia. Interestingly, opening of mitoK_ATP can also trigger cardioprotection. Hearts treated with the mitoK_ATP opener diazoxide for a brief period before ischemia had significantly smaller infarction.^{3 5} The triggering effect from diazoxide can be blocked by protein kinase C^{5 6} and tyrosine kinase inhibitors,³ suggesting that diazoxide activates protein kinases, acting similarly to other triggers. This effect was lost when ROS scavengers were coadministrated with diazoxide.³ ROS are known to activate protein kinases and act as a trigger.² Thus, it was proposed by Pain et al³ that the opening of mitoK_ATP by diazoxide may increase ROS.

In this issue of Circulation Research, Forbes et al⁷ provide a direct demonstration that opening of mitoK_ATP increases ROS production in isolated rat ventricular . . . [Full Text of this Article]

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