Related Experiment Videos
Opening mitochondrial K(ATP) in the heart--what happens, and what does not happen
1Department of Biochemistry and Molecular Biology, Oregon Graduate Institute, Beaverton 97006, USA. garlid@bmb.ogi.edu
Abstract:
There is considerable evidence that opening the mitochondrial ATP-sensitive potassium channel (mitoK(ATP)) is cardioprotective in ischemia-reperfusion. Two prominent questions surround the role of mitoK(ATP) in the cardiomyocyte: How does opening mitoK(ATP) protect? What is the normal physiological role of mitoK(ATP) in the heart? Before these questions can be addressed, it is necessary to agree on the bioenergetic consequences of opening mitoK(ATP), and this distills down to a single question--does opening mitoK(ATP) cause significant uncoupling or not? The evidence strongly indicates that it does not and that reports of uncoupling and inhibition of Ca2+ uptake are the result of using toxic concentrations of K(ATP) channel openers. Thus, opening mitoK(ATP) results in increased K+ flux that is sufficient to change mitochondrial volume but is insufficient to cause significant depolarization of membrane potential. The volume changes, however, have significant bioenergetic consequences for energy coupling in the cell.
Insights
Opening the mitochondrial ATP-sensitive potassium channel (mitoK(ATP)) does not cause significant uncoupling. Instead, it alters mitochondrial volume, impacting cellular energy coupling and offering cardioprotection.
Area of Science:
- Cardiovascular Physiology
- Mitochondrial Biology
- Cellular Bioenergetics
Background:
- Mitochondrial ATP-sensitive potassium channels (mitoK(ATP)) are implicated in cardioprotection during ischemia-reperfusion.
- Key questions remain regarding the protective mechanisms and physiological roles of mitoK(ATP) in cardiomyocytes.
- Clarifying the bioenergetic consequences of mitoK(ATP) opening is crucial for understanding its function.
Purpose of the Study:
- To determine if opening mitoK(ATP) causes significant mitochondrial uncoupling.
- To investigate the bioenergetic consequences of mitoK(ATP) channel activation.
Main Methods:
- Review of existing evidence on mitoK(ATP) channel openers and their effects.
- Analysis of the impact of K+ flux on mitochondrial membrane potential and volume.
- Assessment of bioenergetic consequences related to energy coupling.
Main Results:
- Evidence strongly suggests that opening mitoK(ATP) does not cause significant uncoupling.
- Reported uncoupling and inhibited Ca2+ uptake likely result from using toxic concentrations of channel openers.
- Increased K+ flux alters mitochondrial volume but does not significantly depolarize the membrane potential.
Conclusions:
- Opening mitoK(ATP) does not lead to significant mitochondrial uncoupling.
- MitoK(ATP) activation induces mitochondrial volume changes with significant bioenergetic implications for cellular energy coupling.
- These findings clarify a critical aspect of mitoK(ATP) function in the heart.