Junctophilin 2 is reduced in the border zone 3 hours after a myocardial infarction in sheep heart

Abstract

Eccentric contraction‐induced injury of skeletal muscle is associated with weakness stemming in large part from impaired voltage‐gated sarcoplasmic reticulum Ca2+ release that appears to be mediated by the loss of the triadic protein junctophilin (JP). After a myocardial infarction (MI), the myocytes in the region around the MI (i.e., border zone) appear to be lengthened while activated (i.e., eccentric contraction). If injured by eccentric contractions, these myocytes may contribute to abnormal contractile mechanics, myocardial remodeling and failure. The purpose of this study was to test the hypothesis that JP2 content is reduced in the border zone after an MI in sheep heart. Sheep left anterior descending and second diagonal coronary arteries were ligated for 1 hr followed by 2 hr of reperfusion. Immunoblotting was used to measure JP2 and tubulin content in left ventricular wall samples taken from the infarct (n=5), border zone (n=5), and control remote (n=5) regions. Three hours after inducing the MI, JP2/tubulin ratio is significantly (P<0.05) reduced in infarct (0.28±0.46) and border zone (0.58±0.56) myocardium compared to control remote region (1.52±0.29) of the heart. MI results in the preferential loss of JP2 in the border zone within 3 hours of the MI and may contribute to weakness and abnormal strain in the left ventricular myocardium. .