Restoration of cardiac transient outward potassium current by norepinephrine in diabetic rats

Abstract.

In cardiac ventricle, the density of the transient outward potassium current, I _to, is clearly related to sympathetic nervous system integrity. This sympathetic regulation of I _to expression may be greatly significant to the genesis of cardiac complications of several diseases such us diabetes mellitus. Autonomic neuropathy, including cardiac neuropathy, is a complication of chronic diabetes. The objective of the present study was to identify the possible role of cardiac sympathetic neuropathy in the reduction of I _to current density in diabetic ventricular myocardium. Thus, we employed the patch-clamp technique to test whether I _to can be restored in diabetic myocytes incubated with norepinephrine. We also measured, using HPLC, the catecholamine content of the stellate ganglion, which is responsible for cardiac sympathetic innervation, in normal and diabetic animals. The main result of the present study was to show that a 24-h incubation of diabetic cells with norepinephrine restores I _to density to control values. The restoration of I _to current density by norepinephrine suggests that the diabetes-induced reduction of I _to is at least partially attributable to a reduced trophic effect of norepinephrine on the expression of I _to.