Calcium current in rat diabetic ventricular myocytes

Abstract

The magnitude and kinetics of the L-type calcium current were compared in single left ventricular myocytes isolated from 8-mo-old (8M) and 19-mo-old (19M) genetically diabetic rats (WBN/Kob rats) and age-matched control rats. A diabetic state occurred at 19M but not at 8M. The left ventricular contractility was reduced in 19M WBN/Kob rats compared with age-matched control rats. The duration of the action potential was longer in 19M WBN/Kob rats than in the age-matched control rats. Peak inward current density was similar between diabetic rats and age-matched control rats. In addition, aging did not affect the current density at 8M or 19M. The various kinetic parameters of the L-type calcium current were not different between 19M diabetic and control cell types. The percent increase in the amplitude of the calcium current induced by isoproterenol was less in diabetic cells at the age of 19M, but not at the age of 8M, compared with age-matched control cells. Forskolin (10(-5) M), intracellularly applied adenosine 3',5'-cyclic monophosphate (5 x 10(-5) M), and guanosine 5'-[gamma-thio]triphosphate (10(-4) M) were equally effective in increasing the current in 19M diabetic and age-matched control cell types. The present study demonstrates that the basal calcium current density and kinetic parameters of the current were not altered. However, a decrease in response to beta-stimulation occurred in genetically diabetic rats compared with control rats.

Ionic Mechanisms Underlying Abnormal QT Prolongation and the Associated Arrhythmias in Diabetic Rabbits: A Role of Rapid Delayed Rectifier K⁺ Current

“…I K1 was found unchanged in IDDM [14,[20][21], excluding its contribution to APD prolongation in these animal models of diabetes. I CaL was found smaller in IDMM in some studies [17] but not different in other studies [13,22]. I Na was also found decreased [23].…”

Postrest Contraction in the Ventricular Papillary Muscle of Spontaneously Diabetic WBN/Kob Rat.

“…These findings suggest a dysfunction of the intracellular Ca 2+ handling system in the spontaneously diabetic heart, which is likely to include impaired Ca 2+ sequestration and/or extrusion. The WBN/Kob (Wistar Bonn/Kobori) rat is an inbred strain of Wistar rat in which the male rats develop diabetes between the ages of 9 and 15 months [41,42,44]. Tsuchida et al [41] demonstrated abnormal ventricular function in 8 to 19-month-old male WBN/Kob rats, and showed that these rats resemble the NIDDM model, to some extent, in terms of the slow progression of pathophysiological change and a long span without insulin administration.…”

“…The WBN/Kob (Wistar Bonn/Kobori) rat is an inbred strain of Wistar rat in which the male rats develop diabetes between the ages of 9 and 15 months [41,42,44]. Tsuchida et al [41] demonstrated abnormal ventricular function in 8 to 19-month-old male WBN/Kob rats, and showed that these rats resemble the NIDDM model, to some extent, in terms of the slow progression of pathophysiological change and a long span without insulin administration. Furthermore, Kakinuma et al [18] investigated the time-course of changes in pancreatic fibrosis in WBN/Kob rats.…”

“…In 1976, these rats were brought to Japan by Dr. Kobori and became known as WBN/Kob rats. Now they are known as a model of non-insulin-dependent diabetes mellitus (NIDDM), in which diabetic symptoms (hyperglycemia, glycosuria, polyuria, and glucose intolerance) develop gradually and are rather mild compared with those of STZ-treated diabetic rats [41]. This suggests possible differences of electrophysiological and mechanical properties between STZ-treated diabetic rats and spontaneously diabetic rats.…”

“…This suggests possible differences of electrophysiological and mechanical properties between STZ-treated diabetic rats and spontaneously diabetic rats. It has been reported that male WBN/Kob rats spontaneously develop DM between the ages of 9 and 15 months [41,42,44]. However, acute pancreatitis and the pancreatic fibrosis were found even in 2-3 month-old WBN/Kob rats [18,43].…”