A potent and selective activator of large-conductance Ca 2+ -activated K + channels induces preservation of mitochondrial function after hypoxia and reoxygenation by handling of calcium and transmembrane potential.

Autor: de Souza IIA; Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil.; Programa de Pós-Graduação Em Cardiologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil., da Silva Barenco T; Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil.; Programa de Pós-Graduação Em Cardiologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil., Pavarino MEMF; Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil., Couto MT; Instituto Federal de Educação, Ciência e Tecnologia do Rio de Janeiro, Rio de Janeiro, Brasil., de Resende GO; Instituto Federal de Educação, Ciência e Tecnologia do Rio de Janeiro, Rio de Janeiro, Brasil., de Oliveira DF; Instituto de Bioquímica Médica Leopoldo De Meis, Universidade Federal do Rio de Janeiro, Duque de Caxias, Brasil., Ponte CG; Instituto Federal de Educação, Ciência e Tecnologia do Rio de Janeiro, Rio de Janeiro, Brasil., Nascimento JHM; Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil.; Programa de Pós-Graduação Em Cardiologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil., Maciel L; Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil.; Universidade Federal do Rio de Janeiro, Duque de Caxias, Brasil.
Jazyk: angličtina
Zdroj: Acta physiologica (Oxford, England) [Acta Physiol (Oxf)] 2024 Jun; Vol. 240 (6), pp. e14151. Date of Electronic Publication: 2024 Apr 26.
DOI: 10.1111/apha.14151
Abstrakt: Aims: Ischaemic heart disease remains a significant cause of mortality globally. A pharmacological agent that protects cardiac mitochondria against oxygen deprivation injuries is welcome in therapy against acute myocardial infarction. Here, we evaluate the effect of large-conductance Ca 2+ -activated K + channels (BKCa) activator, Compound Z, in isolated mitochondria under hypoxia and reoxygenation.
Methods: Mitochondria from mice hearts were obtained by differential centrifugation. The isolated mitochondria were incubated with a BKCa channel activator, Compound Z, and subjected to normoxia or hypoxia/reoxygenation. Mitochondrial function was evaluated by measurement of O 2 consumption in the complexes I, II, and IV in the respiratory states 1, 2, 3, and by maximal uncoupled O 2 uptake, ATP production, ROS production, transmembrane potential, and calcium retention capacity.
Results: Incubation of isolated mitochondria with Compound Z under normoxia conditions reduced the mitochondrial functions and induced the production of a significant amount of ROS. However, under hypoxia/reoxygenation, the Compound Z prevented a profound reduction in mitochondrial functions, including reducing ROS production over the hypoxia/reoxygenation group. Furthermore, hypoxia/reoxygenation induced a large mitochondria depolarization, which Compound Z incubation prevented, but, even so, Compound Z created a small depolarization. The mitochondrial calcium uptake was prevented by the BKCa activator, extruding the mitochondrial calcium present before Compound Z incubation.
Conclusion: The Compound Z acts as a mitochondrial BKCa channel activator and can protect mitochondria function against hypoxia/reoxygenation injury, by handling mitochondrial calcium and transmembrane potential.
(© 2024 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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