Myofilament sensitivity to Ca2+ in ventricular myocytes from the Goto-Kakizaki diabetic rat.
The chronic effects of type 2 diabetes mellitus on myofilament sensitivity to Ca(2+) in ventricular myocytes from the Goto-Kakizaki (GK) rat have been investigated. Experiments were performed in ventricular myocytes isolated from 17-month GK rats and age-matched Wistar controls. Myocytes were loaded with fura-2 (an indicator for intracellular Ca(2+) concentration) and the fura-2 ratio (340/380 nm), and shortening were measured simultaneously in electrically stimulated myocytes. Myofilament sensitivity to Ca(2+) was assessed from phase-plane diagrams of fura-2 versus cell length by measuring the gradient of the fura-2-cell length trajectory during late relaxation of the twitch contraction. Non-fasting and fasting blood glucose were elevated in GK rats compared to controls. Fasting blood glucose was 151.5 +/- 15.3 mg/dl (n = 8) in GK rats compared to 72.1 +/- 3.6 mg/dl (n = 9) in controls. At 120 min after intraperitoneal injection of glucose (2 g/kg body weight), blood glucose was 570.8 +/- 36.8 mg/dl in GK rats compared to 148 +/- 8.6 mg/dl in controls. Amplitude of shortening was significantly increased in myocytes from GK rats (6.56 +/- 0.54%, n = 31) compared to controls (5.05 +/- 0.43%, n = 36), and the amplitude of the Ca(2+) transient was decreased in myocytes from GK rats (0.23 +/- 0.02 RU, n = 31) compared to controls (0.30 +/- 0.02 RU, n = 36). The fura-2-cell length trajectory during the late stages of relaxation of the twitch contraction was steeper in myocytes from GK rats (89.2 +/- 16.6 microm/RU, n = 27) compared to controls (31.9 +/- 5.9 microm/RU, n = 35). Increased amplitude of shortening, accompanied by a decrease in amplitude of the Ca(2+) transient, might be explained by an increased myofilament sensitivity to Ca(2+).
Howarth
Frank Christopher
FC
Department of Physiology, Faculty of Medicine & Health Sciences, United Arab Emirates University, Al Ain, UAE. chris.howarth@uaeu.ac.ae
Qureshi
M A
MA
D008841:Actin Cytoskeleton / Q000187:drug effects*; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006352:Heart Ventricles / Q000166:cytology*; D066298:In Vitro Techniques; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008297:Male; D032342:Muscle Cells / Q000187:drug effects* / Q000378:metabolism*; D009200:Myocardial Contraction / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D005947:Glucose; D002118:Calcium