M. Gallego et O. Casis, Regulation of cardiac transient outward potassium current by norepinephrine in normal and diabetic rats, DIABET M R, 17(4), 2001, pp. 304-309
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.