Abstract
Previously, we demonstrated that hypoxic pulmonary vasoconstriction (HPV) of intra-acinar arteries (IAA) requires mitochondrial complex II (= succinate dehydrogenase, SDH) activity (citeauthor ch41:paddenberg2006, Respir Res, 7:93, citeyear ch41:paddenberg2006). Interestingly, SDH subunits A and B have recently been described as components of a multiprotein mitochondrial ATP-sensitive potassium channel (mitoKATP), together with mitochondrial ATP-binding cassette protein-1, adenine nucleotide translocator (ANT), ATP synthase, and phosphate carrier (citeauthor ch41:ardehali2004, Proc Natl Acad Sci USA, 101(32):11880–5, citeyear ch41:ardehali2004). Hence, we tested the hypothesis that such an SDH-containing mitoKATP is involved in HPV. For this purpose, the impact of modulators of mitoKATP on HPV of IAA was studied videomorphometrically in precision cut murine lung slices. Inhibitors of mitoKATP (glibenclamide, 5-hydroxydecanoate) completely suppressed HPV, mitoKATP activators (pinacidil, diazoxide) even induced vasodilatation, and ANT inhibitors (bongkrekic acid, atractyloside) attenuated HPV. This pharmacological profile differs clearly from that described for mitoKATP. Accordingly, co-immunoprecipitation experiments provided no evidence for association of complex II subunits SDH-A, -B and -C with ANT, ATP synthase or cytochrome c oxidase in murine heart mitochondria. Hence, it is likely that the inhibitory effects on HPV that we observed in our experiments result from modulation of several mitochondrial protein complexes independently involved in the signalling cascade such as ROS-producing complex II and ANT-regulated mitochondrial permeability transition pore.
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References
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Paddenberg, R., Faulhammer, P., Goldenberg, A., Gries, B., Heinl, J., Kummer, W. (2009). Impact of Modulators of Mitochondrial ATP-Sensitive Potassium Channel (mitoKATP) on Hypoxic Pulmonary Vasoconstriction. In: Gonzalez, C., Nurse, C.A., Peers, C. (eds) Arterial Chemoreceptors. Advances in Experimental Medicine and Biology, vol 648. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-2259-2_41
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DOI: https://doi.org/10.1007/978-90-481-2259-2_41
Publisher Name: Springer, Dordrecht
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