title: 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.
authors.affiliation: Department of Physiology, School of Pharmacy, University of the Basque Country, Bilbao, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Gallego
authors.forename: E
authors.initials: E
authors.lastname: Casis
authors.forename: M J
authors.initials: MJ
authors.lastname: Izquierdo
authors.forename: O
authors.initials: O
authors.lastname: Casis
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001342:Autonomic Nervous System Diseases / Q000209:etiology / Q000503:physiopathology; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000503:physiopathology*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications; D003929:Diabetic Neuropathies / Q000150:complications / Q000503:physiopathology*; D004553:Electric Conductivity; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006321:Heart / Q000294:innervation*; D006352:Heart Ventricles / Q000503:physiopathology; D009355:Neomycin / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology*; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D004791:Enzyme Inhibitors; D015221:Potassium Channels; D011433:Propranolol; D010738:Type C Phospholipases; D009355:Neomycin; D009638:Norepinephrine; D011224:Prazosin