Myofilament Ca2+ sensitivity in ventricular myocytes from streptozotocin-induced diabetic rat

• Published in: Dubai diabetes and endocrinology journal 2019-03, Vol.9 (3), p.67-74
• Main Authors: Howarth, F.C., Qureshi, M.A.
• Format: Article
• Language: English
• Subjects: Further Section
• ISSN: 2673-1797; 1606-7754; 2673-1738; 2073-5944
• DOI: 10.1159/000497543

Contractile dysfunction is a frequently reported complication of diabetic cardiomyopathy and many of the defects observed in the clinical setting have also been reported in experimentally-induced diabetes. We have investigated the relationship between intracellular Ca 2+ concentration and cell length during the relaxation phase of contraction in ventricular myocytes from streptozotocin (STZ) – induced diabetic rats. Cell length and intracellular Ca 2+ concentration were measured simultaneously in electrically stimulated (1 Hz) myocytes loaded with fura-2 and maintained at 35-36 °C. The amplitude and time to peak shortening and Ca 2+ transient were similar, however, the relaxation of contraction and the Ca 2+ transient were significantly prolonged in myocytes from STZ-treated rats compared to controls. Myofilament Ca 2+ sensitivity, which was assessed by plotting cell length against fura-2 fluorescence ratio during the relaxation phase of a contraction, was significantly increased in myocytes from STZtreated (9.23 ± 0.77 mm/fura-2 fluorescence unit) compare to controls (4.84 ± 0.78 mm/fura-2 fluorescence unit). The slower time course of relaxation of contraction and Ca 2+ transient may be explained by defective sarcoplasmic reticulum Ca 2+ uptake and to a lesser extent mechanisms of plasma membrane Ca 2+ efflux including Na + /Ca 2+ exchange and CaCa 2+ ATPase. In conclusion, the apparent increase in myofilament Ca 2+ sensitivity may be attributed to slower cross-bridge cycling rate which in turn may be related to the alteration of expression of different myofilament myosin isoforms.