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 s odium ion transporters in the rat heart. Intracellular volumes were me asured in isolated hearts by H-1 of water and Co-59 nuclear magnetic r esonance (NMR) of the extracellular marker cobalticyanide; Inhibition of the Na-K-adenosinetriphosphatase pumps with 50 mu M ouabain did not affect the extent of cellular swelling during 30 min of ischemia: cel ls swelled by 0.37 ml/g dry wt compared with the controls (0.38 ml/g d ry wt). After perfusion with 400 mu M ouabain or 200 mu M 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 s odium ion transporters reduced cellular swelling during ischemia: pret reatment (10 min) with 100 mu M furosemide (Na-K-2Cl cotransport), 1.5 mu M ethylisopropylamiloride (Na/H antiport), and 50 mu M 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 contractu re, unlike the data of hearts treated with ouabain and iodoacetate. Th e blockage of each of the passive sodium transporters improved the rec overy of intracellular volumes at reperfusion, indicating that in the heart these pathways are responsible for the sustained reperfusion cel lular edema. It is concluded that acute cellular swelling during myoca rdial ischemia is not caused by insufficiency of the Na-K pumps but is partially mediated by systems that transport sodium into the cells.