Acetylcholine attenuates cardiomyocyte oxidant stress during simulated ischemia and reoxygenation

Bradley C. McPherson, Xiangdong Zhu, Huiping Liu, Bin Wang, Timir Baman, Steven S. McPherson, Mark L A Da Costa, David V. Jayakar, Valluvan Jeevanandam, Zhenhai Yao*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

We wanted to determine whether oxygen radicals open the mitochondrial ATP-dependent potassium channels (KATP) during an ischemic period to reduce cell death and oxidant stress. Chick embryonic cardiomyocytes were used. Cell viability was quantified with propidium iodide (5 μM), and free radicals was measured using 2′,7′-di-chlorofluorescin diacetate. Preconditioning was produced by 10 min of simulated ischemia followed by 10 min of reoxygenation. Acetylcholine (1 mM), infused for 10 min instead of preconditioning, reduced cell death similarly (24 ± 5%, n = 7 and 18 ± 2%, n = 7, respectively, vs. controls, 49 ± 6%, n = 8). In control series, 60 min of simulated ischemia and 3 h of reoxygenation generated free radicals more than 300% above the baseline (ischemia: 3.63 ± 0.58, reoxygenation: 3.66 ± 0.47, n = 8). Preconditioning and acetylcholine markedly attenuated the oxidant stress during simulated ischemia (1.18 ± 0.41, n = 6 and 1.34 ± 0.60, n = 7 vs. controls 3.63 ± 0.58, n = 8) and re-oxygenation (1.23 ± 0.36, n = 6 and 1.50 ± 0.59, n = 7 vs. controls 3.66 ± 0.47, n = 8). The protection of acetylcholine was abolished with pretreatment with the antioxidant thiol reductant 2-mercaptopropionyl glycine and posttreatment with 5-hydroxydecanoate, a selective mitochondrial KATP channel antagonist (37 ± 7%, n = 7). These results demonstrate that oxygen radicals open mitochondrial KATP channels, which mediates the acetylcholine-induced preconditioning effect, and that stimulation of this signaling pathway attenuates oxidant stress.

Original languageEnglish (US)
Pages (from-to)49-56
Number of pages8
JournalPharmacology
Volume64
Issue number1
DOIs
StatePublished - 2002

Keywords

  • Acetylcholine
  • Free radicals
  • K channels
  • Preconditioning

ASJC Scopus subject areas

  • Pharmacology

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