Myofilament Calcium Sensitivity and Cardiac Disease
| العنوان: | Myofilament Calcium Sensitivity and Cardiac Disease |
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| المؤلفون: | Joseph M. Metzger, Faris P. Albayya, Andrea R. Borton, Margaret V. Westfall |
| المصدر: | Circulation Research. 91:525-531 |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2002. |
| سنة النشر: | 2002 |
| مصطلحات موضوعية: | Genetically modified mouse, Gene isoform, Myofilament, medicine.medical_specialty, Heart Diseases, Physiology, Heart Ventricles, Blotting, Western, Biology, Sudden death, Cell Line, Internal medicine, Troponin I, medicine, Animals, Humans, Protein Isoforms, Ventricular Function, Myocyte, Amino Acid Sequence, Cells, Cultured, Cell Size, Hypertrophic cardiomyopathy, Hydrogen-Ion Concentration, medicine.disease, Rats, Actin Cytoskeleton, Endocrinology, Mutation, cardiovascular system, Calcium, Cardiology and Cardiovascular Medicine, Myofibril |
| الوصف: | The heightened Ca 2+ sensitivity of force found with hypertrophic cardiomyopathy (HCM)–associated mutant cardiac troponin I (cTnIR145G; R146G in rodents) has been postulated to be an underlying cause of hypertrophic growth and premature sudden death in humans and in animal models of the disease. Expression of slow skeletal TnI (ssTnI), a TnI isoform naturally expressed in developing heart, also increases myofilament Ca 2+ sensitivity, yet its expression in transgenic mouse hearts is not associated with overt cardiac disease. Gene transfer of TnI isoforms or mutants into adult cardiac myocytes is used here to ascertain if expression levels or functional differences between HCM TnI and ssTnI could help explain these divergent organ-level effects. Results showed significantly reduced myofilament incorporation of cTnIR146G compared with ssTnI or wild-type cTnI. Despite differences in myofilament incorporation, ssTnI and cTnIR146G expression each resulted in enhanced myofilament tension in response to submaximal Ca 2+ under physiological ionic conditions. Myofilament expression of an analogous HCM mutation in ssTnI (ssTnIR115G) did not further increase myofilament Ca 2+ sensitivity of tension compared with ssTnI. In contrast, there was a divergent response under acidic pH conditions, a condition associated with the myocardial ischemia that often accompanies hypertrophic cardiomyopathy. The acidic pH-induced decrease in myofilament Ca 2+ sensitivity was significantly greater in myocytes expressing cTnIR146G and ssTnIR115G compared with ssTnI. These results suggest that differences in pH sensitivities between wild-type ssTnI and mutant TnI proteins may be one factor in helping explain the divergent organ and organismal outcomes in TnI HCM- and ssTnI-expressing mice. |
| تدمد: | 1524-4571 0009-7330 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::439c7d61c42a4d9679333f679cad88aa https://doi.org/10.1161/01.res.0000034710.46739.c0 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....439c7d61c42a4d9679333f679cad88aa |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15244571 00097330 |
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