Decreased myocardial injury and improved contractility after administration of a peptide derived against the alpha-interacting domain of the L-type calcium channel

Background: myocardial infarction remains the leading cause of morbidity and mortality associated with coronary artery disease. the l-type calcium channel (ica-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. methods and 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 ([ca2+]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. © 2014 the authors.