This work involves simultaneous measurement of intracellular pH in rat diaphragm muscle using a weak acid (DMO) and weak base (nicotine) distribution method. Work is currently being performed on the effect of potassium depletion on cell pH and pH heterogeneity. In addition, this is being correlated with in vivo studies of potassium depletion in rats in which cell pH, citrate metabolism and tissue potassium are being correlated. We have already demonstrated that cell pH and pH heterogeneity are affected by changes in metabolism and have postulated that gradients in cell pH may be responsible for metabolic events. In an extension of this work the relationship of cell pH and pH heterogeneity to sodium transport in diaphragm muscle is being studied. Both decreased efflux of sodium from muscle by ouabain and decreased influx by diminished bath sodium concentration will be employed. The relation to metabolism will be investigated by examining diaphragm muscle citrate decarboxylation. This reaction has been shown to be pH sensitive in this tissue. In additon, the action of ethyacrynic acid will be investigated as this diuretic appears to affect pH nicotine independently of pH DMO.