Mitochondrial ATP-sensitive K+ channels prevent oxidative stress, permeability transition and cell death.

Abstract

Ischemia followed by reperfusion results in impairment of cellular and mitochondrial functionality due to opening of mitochondrial permeability transition pores. On the other hand, activation of mitochondrial ATP-sensitive K(+) channels (mitoK(ATP)) protects the heart against ischemic damage. This study examined the effects of mitoK(ATP) and mitochondrial permeability transition on isolated rat heart mitochondria and cardiac cells submitted to simulated ischemia and reperfusion (cyanide/aglycemia). Both mitoK(ATP) opening, using diazoxide, and the prevention of mitochondrial permeability transition, using cyclosporin A, protected against cellular damage, without additive effects. MitoK(ATP) opening in isolated rat heart mitochondria slightly decreased Ca(2+) uptake and prevented mitochondrial reactive oxygen species production, most notably in the presence of added Ca(2+). In ischemic cells, diazoxide decreased ROS generation during cyanide/aglycemia while cyclosporin A prevented oxidative stress only during simulated reperfusion. Collectively, these studies indicate that opening mitoK(ATP) prevents cellular death under conditions of ischemia/reperfusion by decreasing mitochondrial reactive oxygen species release secondary to Ca(2+) uptake, inhibiting mitochondrial permeability transition.

• Authors: Heberty T F Facundo, Juliana G de Paula, Alicia J Kowaltowski
• Journal: Journal of bioenergetics and biomembranes (J Bioenerg Biomembr) Vol. 37 Issue 2 Pg. 75-82 (Apr 2005) ISSN: 0145-479X [Print] United States
• PMID: 15906152 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ATP-Binding Cassette Transporters
• KATP Channels
• Potassium Channels, Inwardly Rectifying
• Reactive Oxygen Species
• uK-ATP-1 potassium channel
• Calcium

Topics

• ATP-Binding Cassette Transporters (physiology)
• Animals
• Calcium (metabolism)
• Cell Death (drug effects)
• Cell Line
• Heart (drug effects)
• KATP Channels
• Male
• Mitochondria, Heart (physiology)
• Myocardium (cytology)
• Oxidative Stress (physiology)
• Permeability
• Potassium Channels, Inwardly Rectifying (physiology)
• Rats
• Rats, Sprague-Dawley
• Reactive Oxygen Species (metabolism)