Furazolidone increases thapsigargin-sensitive Ca(2+)-ATPase in chick cardiac myocytes.
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.
Lax
D
D
Department of Pediatrics, Steele Memorial Children's Research Center, Tucson, Arizona.
Martínez-Zaguilán
R
R
Gillies
R J
RJ
D000818:Animals; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D002642:Chick Embryo; D005664:Furazolidone / Q000494:pharmacology*; D006706:Homeostasis; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009994:Osmolar Concentration; D012964:Sodium / Q000494:pharmacology; D019831:Sodium-Calcium Exchanger; D013729:Terpenes / Q000494:pharmacology*; D019284:Thapsigargin
D002352:Carrier Proteins; D019831:Sodium-Calcium Exchanger; D013729:Terpenes; D005664:Furazolidone; D019284:Thapsigargin; D012964:Sodium; D000252:Calcium-Transporting ATPases; D002118:Calcium