Role of slow delayed rectifier K+-current in QT prolongation in the alloxan-induced diabetic rabbit heart.
OBJECTIVE
In diabetes mellitus, several cardiac electrophysiological parameters are known to be affected. In rodent experimental diabetes models, changes in these parameters were reported, but only limited relevant information is available in other species, having cardiac electrophysiological properties more resembling the human, including the rabbit. The present study was designed to analyse the effects of experimental type 1 diabetes on ventricular repolarization and the underlying transmembrane potassium currents in rabbit hearts.


METHODS
Diabetes was induced by a single injection of alloxan (145 mg kg(-1) i.v.). After the development of diabetes (3 weeks), electrophysiological studies were performed using whole cell voltage clamp and ECG measurements.


RESULTS
The QT(c) interval in diabetic rabbits was moderately but statistically significantly longer than measured in the control animals (155 +/- 1.8 ms vs. 145 +/- 2.8 ms, respectively, n = 9-10, P < 0.05). This QT(c)-lengthening effect of diabetes was accompanied by a significant reduction in the density of the slow delayed rectifier K(+) current, I(Ks) (from 1.48 +/- 0.35 to 0.86 +/- 0.17 pA pF(-1) at +50 mV, n = 19-21, P < 0.05) without changes in current kinetics. No differences were observed either in the density or in the kinetics of the inward rectifier K(+) current (I(K1)), the rapid delayed rectifier K(+) current (I(Kr)), the transient outward current (I(to)) and the L-type calcium current (I(CaL)) between the control and alloxan-treated rabbits.


CONCLUSIONS
It is concluded that type 1 diabetes mellitus, although only moderately, lengthens ventricular repolarization. Diabetes attenuates the repolarization reserve by decreasing the density of I(Ks) current, and thereby may enhance the risk of sudden cardiac death.
Lengyel
Cs
C
Department of Pharmacology & Pharmacotherapy, University of Szeged, Szeged, Hungary.
Virág
L
L
Kovács
P P
PP
Kristóf
A
A
Pacher
P
P
Kocsis
E
E
Koltay
Zs M
ZM
Nánási
P P
PP
Tóth
M
M
Kecskeméti
V
V
Papp
J Gy
JG
Varró
A
A
Jost
N
N
D000496:Alloxan; D000818:Animals; D051668:Delayed Rectifier Potassium Channels / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology*; D004562:Electrocardiography; D006321:Heart; D006329:Heart Conduction System / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D008133:Long QT Syndrome / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D018408:Patch-Clamp Techniques; D011817:Rabbits
D051668:Delayed Rectifier Potassium Channels; D000496:Alloxan