Dexamethasone and cardiac potassium currents in the diabetic rat

Experiments were designed to compare effects of dexamethasone on transient ( I peak ) and sustained ( I sus ) K + currents in control and diabetic rat myocytes. Ventricular myocytes were isolated from control or type 1 streptozotocin (STZ)‐induced diabetic male and female rats. Currents were measured using whole‐cell voltage‐clamp methods. Incubation of cells from control males or females with 100 n M dexamethasone (5–9 h) significantly ( P <0.005) augmented I sus (by 28–31%). I peak was unchanged. I sus augmentation was abolished by cycloheximide or cytochalasin D, but not by inhibition of protein kinases A or C. Inhibition of tyrosine kinases by genistein (but not its inactive analog genistin) prevented the increase of I sus by dexamethasone. In marked contrast, dexamethasone had a significantly ( P <0.015) smaller effect on I sus (11% increase) in cells from male STZ‐diabetic rats, as compared to control cells. However, I sus augmentation in cells from female STZ‐diabetic rats was normal (31% increase). In ovariectomized‐diabetic rats, I sus was unchanged by dexamethasone. The reduced effect in diabetic males might be due to preactivation of tyrosine kinases linking dexamethasone to current modulation. In conclusion, type I diabetes is associated with gender‐specific changes in sensitivity of K + currents to glucocorticoids, linked to alterations in tyrosine‐phosphorylated proteins.British Journal of Pharmacology (2005) 146 , 280–287. doi: 10.1038/sj.bjp.0706314