ATP-sensitive potassium transport in rat brain mitochondria is highly sensitive to mK(ATP) channels openers: a light scattering study

摘要

The aspects of ATP-sensitive K transport regulation by mitochondrial K ,ATP-sensitive (mK ATP ) channels openers are important for understanding the properties of these channels. The effect of K ATP channels openers (KCOs) diazoxide and pinacidil on ATP-sensitive K transport in isolated brain mitochondria was studied in the absence and the presence of MgATP using light scattering technique. Without MgATP we observed high sensitivity of ATP-sensitive K transport to both drugs with full activation at ≤ 0.5 μM. ATP-sensitive K transport was specifically blocked by ATP in the presence of Mg 2 . Neither Mg 2 nor ATP affected V max of ATP-sensitive K transport activated by KCOs, but MgATP shifted the activation curve to micromolar scale. The blockage of ATP-sensitive K transport by K ATP channels blockers glibenclamide and 5-hydroxydecanoate in the absence and the presence of MgATP proved the sensitivity of ATP-sensitive K transport to the blockers of mK ATP channel. Full activation of mK ATP channel by diazoxide and pinacidil on sub-micromolar scale in the absence of MgATP was shown. The sensitivity of ATP-sensitive K transport to the known modulators of mK ATP channel (diazoxide, pinacidil, glibenclamide, 5-HD and MgATP) proved the identity of ATP-sensitive K transport with mK ATP channel activity. Based on our studies, we hypothesized that mK ATP channel might comprise high affinity sites for KCOs binding screened by MgATP. The results of this work reveal novel not described earlier aspects of the regulation of ATP-sensitive K transport by mK ATP channels openers, important for understanding of mK ATP channel properties.