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Lukasiak 2010 Abstract IOC60

From Bioblast
Łukasiak A, Wrzosek A, Chłopicki S, Szewczyk A, Dołowy K (2010) Regulation of endothelial function by large conductance potassium channel opener NS1619. MiPNet15.10.


Lukasiak A, Wrzosek A, Chlopicki S, Szewczyk A, Dolowy K (2010)

Event: MiPNet15.10_IOC60

Endothelial mitochondria are crucial organelles in energetic and regulatory aspects of cell function. It is well documented that in the inner mitochondrial membrane there are various ion channels, among which potassium channels are well known for their protective properties. Activity of large conductance calcium activated potassium channels (BKCa) can be modulated by specific openers such as NS1619 (1,3-dihydro-1-[2-hydroxy-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-2H-benzimidazole-2-one). NS1619 can regulate functioning of endothelial cells EA.hy 926 in many aspects. In our study it was shown that NS1619 changes mitochondrial function both by decreasing mitochondrial potential and by increasing oxygen consumption probably due to activating BKCa channels present in the inner mitochondrial membrane and thus promoting K+ flux. However, other experiments on oxygen consumption show that NS1619 can inhibit Complex I of the respiratory chain. Additionally NS1619 caused increase in calcium concentration within the endothelial cells. Calcium is well known regulator of many signaling pathways within the cells among which activating nitric oxide synthase in endothelial cells is prevalent. Ionophore A23187 (1µM) causes increase in calcium concentration, which subsequently increased nitric oxide (NO) production in EA.hy 926 cells via activation of nitric oxide synthase. Similar activity is proposed for NS1619. Along with these results it was observed that NS1619 increased coronary flow in isolated guinea pig hearts in NO dependent manner (100 µM L-NAME, inhibitor of nitric oxide synthase, partially reversed the effect of NS1619). It seems that NS1619 can have beneficial effect on endothelium via vasodilating activity, however, the exact mechanism which seems to involve both BKCa channel activation and other places of action, needs further investigation.

Keywords: Endothelium, mitochondria, mitochondrial potassium channels

O2k-Network Lab: PL Warsaw Szewczyk A


Stress:Mitochondrial disease  Organism: Guinea pig  Tissue;cell: Heart, Endothelial;epithelial;mesothelial cell