Volume-related activities of sodium ion transporters: multinuclear NMR studies of isolated rat hearts.

The present study aims to determine the volume-related activities of sodium ion transporters in the rat heart. Intracellular volumes were measured in isolated hearts by 1H of water and 59Co nuclear magnetic resonance (NMR) of the extracellular marker cobalticyanide. Inhibition of the Na-K-adenosinetriphosphatase pumps with 50 microM ouabain did not affect the extent of cellular swelling during 30 min of ischemia: cells swelled by 0.37 ml/g dry wt compared with the controls (0.38 ml/g dry wt). After perfusion with 400 microM ouabain or 200 microM iodoacetate, the cells shrank during ischemia (from 2.50 +/- 0.06 to 2.20 +/- 0.09 and 2.28 +/- 0.07 ml/g dry wt, respectively). Inhibition of passive sodium ion transporters reduced cellular swelling during ischemia: pretreatment (10 min) with 100 microM furosemide (Na-K-2Cl cotransport), 1.5 microM ethylisopropylamiloride (Na/H antiport), and 50 microM lidocaine (sodium channels) led to swelling of 0.27, 0.21, and 0.13 ml/g dry wt, respectively. The extent of cellular water accumulation was apparently correlated with the onset and maximal force of the ischemic contracture, unlike the data of hearts treated with ouabain and iodoacetate. The blockage of each of the passive sodium transporters improved the recovery of intracellular volumes at reperfusion, indicating that in the heart these pathways are responsible for the sustained reperfusion cellular edema. It is concluded that acute cellular swelling during myocardial ischemia is not caused by insufficiency of the Na-K pumps but is partially mediated by systems that transport sodium into the cells.