CHRONIC DIABETES-MELLITUS PROLONGS ACTION-POTENTIAL DURATION OF RAT VENTRICULAR MUSCLES - CIRCUMSTANTIAL EVIDENCE FOR IMPAIRED CA-2+ CHANNEL

Study objective - The aim of the study was to investigate the effects of chronic diabetes mellitus on electromechanical properties of ventricular papillary muscles.Design - Conventional glass microelectrodes and tension recording techniques were used in isolated hearts of rats made diabetic for 30-40 weeks by single intravenous injections of streptozotocin.Subjects - Experimental animals were male Wistar rats of 200-250 g. Diabetic rats (n = 14) were given streptozotocin 65 mg·kg-1; controls (n = 15) were given vehicle only.Measurements and main results - (1) The maximum upstroke velocity of the action potential duration of diabetic muscles was decreased compared to control, with no difference in the resting potential. (2) At all stimulation frequencies (0.2, 1 and 5 Hz), and particularly the lower ones, the action potential duration of diabetic muscles was longer than control. (3) In diabetic muscles, frequency dependent shortening of the late phase of action potential duration (APD75, APD90) was more pronounced, and frequency dependent lengthening of the early phase (APD25, APD50) was less pronounced. (4) A blocker of transient outward current, 4-aminopyridine, lengthened the early phase of action potential durations by the same amount in diabetic and control muscles. (5) A Ca2+ channel blocker, CoCl2, dramatically shortened all levels of action potential duration, with much greater effect on diabetic muscles. (6) Ryanodine lengthened the early phase of action potential duration and shortened the late phase in both diabetic and control muscles. It enhanced the difference between the groups in the early phase. (7) Developed tension in the presence of ryanodine (ryanodine resistant tension component) was greater in diabetic muscles than in control.Conclusions - The findings suggest that altered Ca2+ current, but not altered Na+-Ca2+ exchange current or altered transient outward current, significantly prolongs action potential duration in diabetic rat ventricular muscles.