title: Decreased myocardial injury and improved contractility after administration of a peptide derived against the alpha-interacting domain of the L-type calcium channel.
abstract: BACKGROUND
  Myocardial infarction remains the leading cause of morbidity and mortality associated with coronary artery disease. The L-type calcium channel (IC a-L) is critical to excitation and contraction. Activation of the channel also alters mitochondrial function. Here, we investigated whether application of a alpha-interacting domain/transactivator of transcription (AID-TAT) peptide, which immobilizes the auxiliary β2 subunit of the channel and decreases metabolic demand, could alter mitochondrial function and myocardial injury.
  
  
  RESULTS
  Treatment with AID-TAT peptide decreased ischemia-reperfusion injury in guinea-pig hearts ex vivo (n=11) and in rats in vivo (n=9) assessed with uptake of nitroblue tetrazolium, release of creatine kinase, and lactate dehydrogenase. Contractility (assessed with catheterization of the left ventricle) was improved after application of AID-TAT peptide in hearts ex vivo (n=6) and in vivo (n=8) up to 12 weeks before sacrifice. In search of the mechanism for the effect, we found that intracellular calcium ([Ca(2+)]i, Fura-2), superoxide production (dihydroethidium fluorescence), mitochondrial membrane potential (Ψm, JC-1 fluorescence), reduced nicotinamide adenine dinucleotide production, and flavoprotein oxidation (autofluorescence) are decreased after application of AID-TAT peptide.
  
  
  CONCLUSIONS
  Application of AID-TAT peptide significantly decreased infarct size and supported contractility up to 12 weeks postcoronary artery occlusion as a result of a decrease in metabolic demand during reperfusion.
authors: School of Anatomy, Physiology and Human Biology, The University of Western Australia, Crawley, WA, Australia (H.M.V., L.C.H.).
authors: Helena M
authors: HM
authors: Viola
authors: Department of Physiology, David Geffen School of Medicine at UCLA, Los Angeles, CA (M.C.J., K.P.R.).
authors: Maria C
authors: MC
authors: Jordan
authors: Department of Physiology, David Geffen School of Medicine at UCLA, Los Angeles, CA (M.C.J., K.P.R.).
authors: Kenneth P
authors: KP
authors: Roos
authors: School of Anatomy, Physiology and Human Biology, The University of Western Australia, Crawley, WA, Australia (H.M.V., L.C.H.).
authors: Livia C
authors: LC
authors: Hool
mesh_terms: D000818:Animals; D002118:Calcium / Q000032:analysis; D020746:Calcium Channels, L-Type / Q000187:drug effects* / Q000494:pharmacology / Q000502:physiology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003402:Creatine Kinase / Q000378:metabolism; D004195:Disease Models, Animal; D006168:Guinea Pigs; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D009203:Myocardial Infarction / Q000188:drug therapy; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D013481:Superoxides / Q000032:analysis
chemical_list: C000595452:AID-TAT peptide; D020746:Calcium Channels, L-Type; D002316:Cardiotonic Agents; D010446:Peptide Fragments; D013481:Superoxides; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase; D002118:Calcium
keywords: ion channels; ischemia; peptides; reperfusion