The Effects of Metabolic Inhibitors on Cultured Rat Heart Cells

Cells derived from neonatal rat heart tissue may be cultured in vitro. These cells retain the ability to spontaneously beat or contract. As the cells age in vitro, the beating rate gradually decreases and eventually stops . This loss of function has been described as dedifferentiation (1) . In the intact, adult, mammalian heart, lipids are the primary source of metabolic energy (2) . Lipids are also required for the maintenance of beating in cultured heart cells ; if lipids are removed from the growth medium, the cells lose the ability to beat (3) . However, neonatal rat heart tissue is largely dependent on glucose metabolism (4) . As the heart cells age in vitro, there is a shift in the respiratory quotient (RQ) from 0 .86 at day 0 to 0.96 at day 14. This suggests that the heart cells switch from lipid to carbohydrate metabolism as they age in vitro (5) . Glucose metabolism via the pentose phosphate pathway has been demonstrated in chick heart embryos (6) and in cultured heart cells (7) . The glycolytic pathway for glucose metabolism is also functional in cultured rat heart cells (5) . Glucose metabolism in a number of cells and animal tissues is inhibited by the glucose analog, 2-deoxy-D-glucose (8, 9) . This compound is transported into the cell (10) where it is phosphorylated by hexokinase to form 2-deoxyglucose-6-phosphate. This compound then acts as a competitive inhibitor of the glycolytic enzyme, phosphoglucoisomerase (8, 11) . An inhibitory effect of 2-deoxyglucose-6-phosphate on glucose-6-phosphate dehydrogenase has also been reported (8) .