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 (I(C)(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 β(2) 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 ([Ca(2+)](i), Fura‐2), superoxide production (dihydroethidium fluorescence), mitochondrial membrane potential (Ψ(m), 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.