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 curr ent, responsible for action potential duration in the rat and human. Beside s, diabetes alters cardiac inotropic responses to sympathetic innervation, and this can result from altered responsiveness of the transient outward cu rrent to norepinephrine. Methods Transient outward K+ current was measured using the whole-cell conf iguration of the patch-clamp technique. Myocytes were isolated from the rig ht ventricle of healthy and streptozotocin-induced diabetic rats. Results Norepinephrine, through alpha (1)-adrenoceptors, reduces current am plitude in a concentration-dependent way, with no effects on current kineti cs or voltage dependence of inactivation. Diabetes reduces current amplitud e and accelerates its inactivation process. Norepinephrine also reduces cur -rent amplitude in diabetic cells; however diabetes shifts to the right the concentration-response curve and reduces the maximum effect of the neurotr ansmitter. Conclusions Norepinephrine reduces the amplitude of isolated ventricular tr ansient outward K+ current with no effects on current properties in myocyte s isolated from either healthy or diabetic hearts. Diabetes shifts the conc entration-response curve; thus diabetic myocytes are more resistant to symp athetic regulation than are healthy cells. Copyright (C) 2001 John Wiley & Sons, Ltd.