Altered ca2+ handling in ventricular myocytes isolated from
diabetic rats.
Lagadic-Gossmann, D., K. J. Buckler, K. Le Prigent & D. Feuvray.
Laboratoire de Physiologie Cellulaire, ERS CNRS 100,
Universit[acute]e Paris-Sud, B[circumflex]at. 443, 91405 Orsay cedex,
France
APStracts 2:0434H, 1995.
It has been suggested that alterations of intracellular Ca2+
homeostasis may be responsible for the development of diabetic
cardiomyopathy. We have studied the effects of streptozotocin-induced
diabetes upon intracellular calcium concentration ([Ca2+]i) in
enzymically isolated, rat ventricular myocytes. [Ca2+]i was measured
using indo-1 or fluo-3. Both diastolic [Ca2+]i and peak systolic
[Ca2+]i were reduced in diabetic, compared to normal, myocytes (by
52% and 43%, respectively). The decay phase of the systolic [Ca2+]i
transient was slower in the diabetic myocyte compared to normal (time
constant = 89.6 +/- 3.4 ms, n= 23, normal vs. 105.2 +/- 4.05 ms,
n=20, diabetic; P<0.01). This led to a significant prolongation
of the [Ca2+]i-transient duration in the diabetic myocyte. In both
normal and diabetic myocytes, increasing the frequency of electrical
stimulation decreased peak systolic [Ca2+]i. The relationship between
stimulation frequency and normalised peak systolic [Ca2+]i was the
same for both normal and diabetic myocytes. We also found that the
caffeine-induced Ca2+ release (used as an index of the sarcoplasmic
reticulum (SR) Ca2+ content) was significantly reduced in diabetic
myocytes. These data indicate that SR calcium content is decreased by
diabetes. In the presence of thapsigargin (2.5 [mu]M, an inhibitor of
SR Ca2+-ATPase) the magnitude and time course of stimulus evoked
[Ca2+]i-transients were identical in both groups of myocytes
suggesting that Ca2+-influx/efflux across the plasma membrane are not
significantly affected in diabetes. We conclude that: a) diabetes is
associated with significant alterations in [Ca2+]i homeostasis; and
b) that the decrease in systolic [Ca2+]i and lengthening of the
systolic [Ca2+]-transient result primarily from dysfunction of the
SR.
Received 11 April 1995; accepted in final form 25 September 1995.
APS Manuscript Number H358-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95