Quick Search 
Methods and Findings
Register or sign in

  
 
  
Methods Find Exp Clin Pharmacol 2010, 32(2): 107
ISSN 0379-0355
Copyright 2010 Clarivate Analytics
CCC: 0379-0355
DOI: 10.1358/mf.2010.32.2.1428738
 
 
Mitochondrial pores modulate the protective effect of acetylcholine on ventricular myocytes during ischemia/reperfusion injury
Sun, G.-Q., Wang, J., Li, Q., Ye, Z.-G., Xia, Q.
 
 
In this study, we investigated the cardioprotective effect of acetylcholine (ACh) via modulation of mitochondrial permeability transition pore (MPTP) opening through the mitochondrial ATP-sensitive potassium channel (mitoKATP channel). In isolated ventricular myocytes from male Sprague-Dawley rats, 0.1 µmol/L ACh was administered for 6 min, before 30 min of simulated ischemia and 30 min of reperfusion (I/R). A mitoKATP inhibitor (5-hydroxydecanoate, 5-HD) and an MPTP opener (atractyloside, Atr) were used to analyze the underlying mechanisms. Myocyte contractile function, myocyte viability, lactate dehydrogenase (LDH) release, reactive oxygen species (ROS) and mitochondrial membrane potential were assayed. During reperfusion, the amplitudes of contraction, ±dL/dtmax, and end-diastolic length of myocytes were decreased, which were markedly improved by pretreatment with ACh. However, such effects of ACh were reversed by 100 µmol/L 5-HD for 20 min before ischemia, or 20 µmol/L Atr for 20 min at the beginning of reperfusion. Pretreatment with ACh markedly reduced I/R-induced cell death, LDH release, ROS signals and mitochondrial membrane potential dissipation, all of which were reversed by 5-HD or Atr. In conclusion, ACh may protect ventricular myocytes from I/R injury by inhibiting MPTP opening and stabilizing the mitochondrial membrane potential through activating the mitoKATP channel.


Full Text: HTMLPDF 
 
  



© Clarivate Analytics. All rights reserved.
Copyright NoticeTerms of UsePrivacy StatementCookie Policy