Aims: 

The ATP-regulated potassium channel (mitoK_ATP channel) is present in the inner membrane of heart mitochondria. The purpose of the study was to analyze regulation of mitochondrial potassium channels by ATP, pH and pharmacological modulators.

Methods: 

In this study a single channel activity was measured after reconstitution of the inner mitochondrial membrane from bovine myocardium into planar lipid bilayer.

Results: 

We provide direct evidence of vectorial pH regulation of mitoK_ATP channels. Alkalization (from pH 7.2 to 8.2) of the matrix side changed the channel conductance, open probability, mean open and closed dwell time distribution. The effect was reversed by changing pH back to the neutral value. The mitoK_ATP channel activity was not changed by alkalization of the cytosolic side of the planar lipid bilayer. Additionally, we observed that acidification from pH 7.2 to 6.2 in either the matrix or cytosolic compartments decreases the open probability of the channel. This effect is reversed by perfusion with pH 7.2 medium. Additionally, our results suggest that the mitoK_ATP channel is regulated by multiple phosphorylation events. The mitoK_ATP channel "run-down" was reversed by incubation with ATP/ Mg²⁺ complex on both sides of the planar lipid bilayer.

Conclusion: 

We conclude that pH and ATP play an important regulatory role for the cardiac mitoK_ATP channel with respect to ischaemia-reperfusion phenomena.

Supported by Polish Mitochondrial Network and grant from Ministry of Research and Higher Education N301 05331/1676