Regulation of cardiac transient outward potassium current by norepinephrine in normal and diabetic rats.
BACKGROUND
Alpha-adrenergic stimulation regulates cardiac contractility by reducing repolarising K+ currents. Despite this, no published work exists on the effects of norepinephrine on isolated cardiac transient outward current, responsible for action potential duration in the rat and human. Besides, diabetes alters cardiac inotropic responses to sympathetic innervation, and this can result from altered responsiveness of the transient outward current to norepinephrine.


METHODS
Transient outward K+ current was measured using the whole-cell configuration of the patch-clamp technique. Myocytes were isolated from the right ventricle of healthy and streptozotocin-induced diabetic rats.


RESULTS
Norepinephrine, through alpha(1)-adrenoceptors, reduces current amplitude in a concentration-dependent way, with no effects on current kinetics or voltage dependence of inactivation. Diabetes reduces current amplitude and accelerates its inactivation process. Norepinephrine also reduces current amplitude in diabetic cells; however diabetes shifts to the right the concentration-response curve and reduces the maximum effect of the neurotransmitter.


CONCLUSIONS
Norepinephrine reduces the amplitude of isolated ventricular transient outward K+ current with no effects on current properties in myocytes isolated from either healthy or diabetic hearts. Diabetes shifts the concentration-response curve; thus diabetic myocytes are more resistant to sympathetic regulation than are healthy cells.
Gallego
M
M
Department of Physiology, School of Pharmacy, University of the Basque Country, PO Box 699, 48080 Bilbao, Spain.
Casis
O
O
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004553:Electric Conductivity; D006321:Heart / Q000503:physiopathology*; D008564:Membrane Potentials; D009638:Norepinephrine / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000502:physiology*; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000502:physiology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D015221:Potassium Channels; D018340:Receptors, Adrenergic, alpha-1; D011433:Propranolol; D011188:Potassium; D009638:Norepinephrine; D011224:Prazosin