Intracellular protons in ventricular myocytes from diabetic
rats.
Xu, Zhi, Kaushik P. Patel, George J. Rozanski.
Department of Physiology and Biophysics, University of Nebraska
Medical Center, Omaha, Nebraska, 68198-4575
APStracts 3:0251H, 1996.
The purpose of this study was to examine the effects of protons on
cardiac ion channel function in early stages of diabetes mellitus.
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 streptozotocin-induced diabetic and
control rats. Proton concentration was controlled by independently
varying the pH of buffered external or pipette (pHp) solutions.
External acidification did not alter Ito in diabetic rat myocytes
when initiated after intracellular dialysis with standard pHp 7.2,
but when these cells were dialyzed with acidic pHp (6.6 or 6.0), Ito
density was significantly reduced. Low pHp also reduced Ito density
more in cells from diabetic rats than in controls, whereas alkaline
pHp had no effect on either group of cells compared with standard pHp
7.2. In control myocytes dialyzed with pHp 6.0, block of Na+/H+
exchange with 5-(N,N-Dimethyl)-amiloride (DMA) or Na+-free external
solution further reduced Ito density compared with pHp 6.0 alone,
whereas these treatments had less of an effect on acid-dialyzed cells
from diabetic rats. Dialysis with pHp to 6.0 did not alter IK1 in
either group of cells compared with standard pHp 7.2, but when done
in the presence of DMA or Na+-free conditions, IK1 density in both
groups was significantly reduced by nearly the same amount. We
conclude that intracellular protons inhibit Ito channels in
ventricular myocytes from diabetic and control rats, but that for a
given acid load, inhibition is markedly greater in diabetics. This
difference may be explained by a diabetes-induced decrease in Na+/H+
exchange that limits proton extrusion during intracellular acidosis.
Moreover, acidosis may differentially suppress Ito and IK1,
suggesting that these K+ channels exhibit dissimilar sensitivities to
intracellular protons.
Received 10 January 1996; accepted in final form 20 May 1996.
APS Manuscript Number H9-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 28 June 96