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

Abstract

In cardiac ventricle, the density of the transient outward potassium current, Ito, is clearly related to sympathetic nervous system integrity. This sympathetic regulation of Ito 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 Ito current density in diabetic ventricular myocardium. Thus, we employed the patch-clamp technique to test whether Ito 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 Ito density to control values. The restoration of Ito current density by norepinephrine suggests that the diabetes-induced reduction of Ito is at least partially attributable to a reduced trophic effect of norepinephrine on the expression of Ito.

α1-Adrenoceptors stimulate a Gαs protein and reduce the transient outward K+ current via a cAMP/PKA-mediated pathway in the rat heart

“…In the present work, ␣ 1 -adrenoceptor stimulation decreased I to in rat ventricular myocytes as previously described (4,17,18,23,29,32,43). The major findings of this study are that ␣ 1 -adrenoceptor stimulation activates G ␣s proteins and inhibits I to via a cAMP/PKA-mediated signaling pathway.…”

Depressed transient outward potassium current density in catecholamine-depleted rat ventricular myocytes

“…It has been reported that chronic conditioning of noninnervated myocytes with NPY simulates the effect of sympathetic innervation by inducing an ␣-inhibitory response to phenylephrine (39) and that NPY affects the functional expression of the adrenergic signaling cascade (37). In our model, micromolar concentrations of norepinephrine did not restore I to to control values, as reported for other model of denervation (13,14). We investigated whether NPY helped to restore I to in the presence of a low concentration of norepinephrine; no effect was observed in control conditions.…”

“…We investigated whether the decrease in I to observed in reserpine-treated rats could be restored by long-term application of norepinephrine as described in other animal models where a decrease in I to was associated with denervation (13). Myocytes from control and reserpine-treated animals were maintained in 0.5 mM CaCl 2 -Tyrode solution.…”

Monoamine Oxidase A Activity and Norepinephrine Level in Hippocampus Determine Hyperwheel Running in SPORTS Rats

“…In general, abnormal levels of striatal DA in humans or animals are associated with changes in emotional and motivational behavior (Rhodes et al, 2003;Leng et al, 2004). We measured DA concentrations in the rat striatum, where a large number of dopaminergic neurons exist (Gallego et al, 2003;Leng et al, 2004). However, there was no significant change in the striatal DA and its metabolite levels in the extracellular fluid or tissue homogenates of SPORTS rats.…”

“…Whether hippocampal NE induces voluntary wheel running has not yet been clarified, although genetically or pharmacologically enhanced NE level in brain regions that include the hippocampus increases field locomotor activity in experimental animals (Xu et al, 2000;Cryan et al, 2004;Shishikina et al, 2004;Lahdesmaki et al, 2003;Cases et al, 1995). Given the fact that obese and diabetic animals with low physical activity have less NE in the hippocampus than normal controls (Gallego et al, 2003;Yamato et al, 2004;Lackovic et al, 1990), we hypothesized that hippocampal NE is involved in the initiation of voluntary exercise.…”