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The purpose of this study was to investigate functional cellular defects present in adult cardiac myocytes expressing mutant \u03b4-sarcoglycans harboring the dominant inherited DCM mutations R71T or R97Q. This study demonstrates that DCM mutant \u03b4-sarcoglycans can be stably expressed in adult rat cardiac myocytes and traffic similarly to wild-type \u03b4-sarcoglycan to the plasma membrane, without perturbing assembly of the dystrophin-glycoprotein complex. However, expression of DCM mutant \u03b4-sarcoglycan in adult rat cardiac myocytes is sufficient to alter cardiac myocyte plasma membrane stability in the presence of mechanical strain. Upon cyclical cell stretching, cardiac myocytes expressing mutant \u03b4-sarcoglycan R97Q or R71T have increased cell-impermeant dye uptake and undergo contractures at greater frequencies than myocytes expressing normal \u03b4-sarcoglycan. Additionally, the R71T mutation creates an ectopic N-linked glycosylation site that results in aberrant glycosylation of the extracellular domain of \u03b4-sarcoglycan. Therefore, appropriate glycosylation of \u03b4-sarcoglycan may also be necessary for proper \u03b4-sarcoglycan function and overall dystrophin-glycoprotein complex function. These studies demonstrate that DCM mutations in \u03b4-sarcoglycan can exert a dominant negative effect on dystrophin-glycoprotein complex function leading to myocardial mechanical instability that may underlie the pathogenesis of \u03b4-sarcoglycan-associated DCM.<\/jats:p><jats:p>Listen to this article's corresponding podcast at http:\/\/ajpheart.podbean.com\/e\/dilated-cardiomyopathy-delta-sarcoglycan-mutations-cause-cardiomyocyte-membrane-instability\/ .<\/jats:p>","DOI":"10.1152\/ajpheart.00521.2015","type":"journal-article","created":{"date-parts":[[2016,3,12]],"date-time":"2016-03-12T04:32:59Z","timestamp":1457757179000},"page":"H1140-H1150","source":"Crossref","is-referenced-by-count":17,"title":["Dilated cardiomyopathy mutations in \u03b4-sarcoglycan exert a dominant-negative effect on cardiac myocyte mechanical stability"],"prefix":"10.1152","volume":"310","author":[{"given":"Matthew D.","family":"Campbell","sequence":"first","affiliation":[{"name":"Department of Molecular 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