AJP - Heart and Circulatory Physiology, Vol 267, Issue 2 734-H741, Copyright © 1994 by American Physiological Society
Furazolidone increases thapsigargin-sensitive Ca(2+)-ATPase in chick cardiac myocytes
D. Lax, R. Martinez-Zaguilan and R. J. Gillies
Department of Pediatrics, Steele Memorial Children's Research Center, Tucson, Arizona.
Furazolidone is a nitrofuran antibiotic that causes dilated cardiomyopathy
in turkeys and chicks and serves as an important model of human dilated
cardiomyopathy. The mechanism by which furazolidone produces cardiac injury
remains unknown. We investigated the hypothesis that furazolidone alters
Ca2+ homeostasis in cardiac muscle cells. Myocytes harvested from 7-day-old
chick embryos were treated with furazolidone (0.02, 0.1, and 1 mM) for
24-52 h and then coloaded with seminaphthorhodafluor-1 (SNARF 1) and fura 2
to measure simultaneously intracellular pH (pHi) and intracellular Ca2+
concentration ([Ca2+]i), respectively. Furazolidone did not affect
steady-state [Ca2+]i levels in cardiac myocytes. Na+ removal was associated
with a rapid increase in [Ca2+]i due to the Na+/Ca2+ exchanger, which was
similar in control and furazolidone-treated cells. The rate of [Ca2+]i
recovery after Na+ removal was significantly increased in the
furazolidone-treated cells compared with controls. In most cells, recovery
from Ca2+ load is accomplished by the activity of
Ca(2+)-adenosinetriphosphatases (ATPases). Thapsigargin, inhibitor of
sarcoplasmic reticulum Ca(2+)-ATPase, prevented the furazolidone-induced
changes. These results demonstrate that furazolidone increases the activity
of thapsigargin-sensitive Ca(2+)-ATPase without affecting Na+/Ca2+
exchange. These data enhance our understanding of the mechanism of
furazolidone-induced injury in cardiac myocytes and may be useful in
determining mechanisms of injury in dilated cardiomyopathy.
