Regulation of cardiac transient outward potassium current by norepinephrine in normal and diabetic rats

Publisher Website
Google Scholar
Abstract
Background α‐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 α1‐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. Copyright © 2001 John Wiley & Sons, Ltd.