Metabolic basis of decreased transient outward k+ current in
ventricular myocytes from diabetic rats.
Xu, Zhi, Kaushik P. Patel, and George J. Rozanski.
Department of Physiology and Biophysics, University of Nebraska
Medical Center, Omaha, Nebraska, 68198-4575
APStracts 3:0337H, 1996.
The purpose of this study was to examine the mechanisms of alterations
in cardiac K+ channel function in early stages of experimental
diabetes mellitus induced by streptozotocin. Transient outward (Ito)
and inward rectifier (IK1) K+ currents were recorded by the whole
-cell, voltage-clamp technique in ventricular myocytes isolated from
hearts of 2-4 week diabetic and age-matched control rats. Ito density
in myocytes from diabetic rats was approximately 30% less than
control (at +60 mV; p < 0.01) under basal recording conditions
in the presence of 18 mM external glucose, whereas IK1 density was
not different between groups. When external glucose concentration was
decreased to 5 mM for 4-6 hrs, basal Ito density was not changed in
either group of myocytes. To further examine the possible metabolic
basis of reduced Ito density in myocytes from diabetic rats, we
separately tested three structurally different compounds that affect
substrate utilization in cardiac myocytes: insulin (0.1 [mu]M),
dichloroacetate (1.5 mM), and L-carnitine (10 mM). Each compound
completely normalized Ito density in myocytes from diabetic rats
treated in vitro for 4-6 hrs. The same agents had no effect on Ito
density in control myocytes nor was IK1 altered in either group of
cells. These data provide the first evidence to support the
hypothesis that there is a metabolic basis for decreased Ito density
in diabetic rat ventricular myocytes in early stages of this model.
Furthermore, our data suggest that depressed glucose metabolism in
the diabetic heart may be a key factor underlying changes in Ito
channel function, since agents that increase glucose utilization
normalize Ito density within a short time period.
Received 3 June 1996; accepted in final form 1 August 1996.
APS Manuscript Number H496-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 29 August 1996