FURAZOLIDONE INCREASES THAPSIGARGIN-SENSITIVE CA2-ATPASE IN CHICK CARDIAC MYOCYTES()

Furazolidone is a nitrofuran antibiotic that causes dilated cardiomyop athy in turkeys and chicks and serves as an important model of human d ilated cardiomyopathy. The mechanism by which furazolidone produces ca rdiac injury remains unknown. We investigated the hypothesis that fura zolidone alters Ca2+ homeostasis in cardiac muscle cells. Myocytes har vested 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 seminaphthorhoda fluor-1 (SNARF 1) and fura 2 to measure simultaneously intracellular p H (pH(i)) and intracellular Ca2+ concentration ([Ca2+](i)), respective ly. Furazolidone did not affect steady-state [Ca2+](i) levels in cardi ac myocytes. Na+ removal was associated with a rapid increase in [Ca2](i) due to the Na+/Ca2+ exchanger, which was similar in control and f urazolidone-treated cells. The rate of [Ca2+](i) recovery after Na+ re moval was significantly increased in the furazolidone-treated cells co mpared with controls. In most cells, recovery from Ca2+ load is accomp lished by the activity of Ca2+-adenosinetriphosphatases (ATPases). Tha psigargin, inhibitor of sarcoplasmic reticulum Ca2+-ATPase, prevented the furazolidone-induced changes. These results demonstrate that furaz olidone increases the activity of thapsigargin-sensitive Ca2+-ATPase w ithout affecting Na+/Ca2+ exchange. These data enhance our understandi ng of the mechanism of furazolidone-induced injury in cardiac myocytes and may be useful in determining mechanisms of injury in dilated card iomyopathy.