Heart mitochondria contain functional ATP-dependent K+ channels

Area of Science:

• Cardiovascular Physiology
• Mitochondrial Biology
• Ion Channel Research

Background:

• Recent studies questioned the existence and functional significance of mitochondrial ATP-dependent potassium (mitoK(ATP)) channels.
• Understanding these channels is crucial for cellular energy metabolism and cardiac function.

Purpose of the Study:

• To confirm the presence and composition of mitoK(ATP) channels in mouse heart mitochondria.
• To investigate the functional impact of channel openers and blockers on mitochondrial membrane potential.

Main Methods:

• Western blotting and immunogold electron microscopy to identify K(ATP)-channel subunits (Kir6.1, Kir6.2, SUR1, SUR2) in isolated mitochondria.
• BODIPY-glibenclamide labeling to detect sulfonylurea binding.
• Confocal imaging with MitoFluorRed to assess mitochondrial membrane potential in isolated respiring heart mitochondria.

Main Results:

• Kir6.1 and Kir6.2 proteins were detected in mitochondria, while SUR1 and SUR2 were absent.
• A SUR2-like band and mitochondrial-transport tags were identified in Kir6.1/Kir6.2 sequences.
• Glibenclamide altered mitochondrial membrane potential; diazoxide and BMS-191095 reversed this effect, indicating functional channel activity.

Conclusions:

• A functional K(ATP) channel is present in heart mitochondria.
• This channel comprises Kir6.1 and Kir6.2 subunits and is modulated by specific openers like diazoxide and BMS-191095.
• Mitochondrially generated peroxynitrite acts as a physiological channel opener.