Substrate-selective maintenance of tissue K+ in perfused rat kidney

We sought to determine in the functioning, substrate-limited, isolated perfused rat kidney whether there is substrate selectivity for maintenance of renal tissue K+ content (mueq/g dry wt). The kidney was perfused for 75 min with 6 g/100 ml substrate-free albumin in Krebs-Ringer bicarbonate (pH approximately 7.4) in the absence of exogenous substrate (control) or in the presence of one substrate (usually 5 mM) chosen from three groups of substrates: 1) substrates of the glycolytic pathway: glucose, fructose, and glycerol; 2) precursors of or substrates of the tricarboxylic acid cycle: citrate (2 mM), alpha-ketoglutarate, succinate, glutamine, glutamate, and acetate; 3) substrates selectively used by the kidney for synthetic work: glycine and inositol. A significant loss of tissue K+ occurred during perfusion in the absence of exogenous substrate (-17%) and also during perfusion with inositol, glycine, acetate, glutamine, or glycerol. No loss of tissue K+ occurred in the presence of fructose, citrate, alpha-ketoglutarate, succinate, or glutamate. Glucose was unique in that at 10 mM, but not at 5 mM, a loss of tissue K+ occurred. We conclude that there is substrate-selective support of renal tissue K+ content, and that those substrates known to enter principally into energy-requiring biosynthetic pathways do not maintain tissue K+ content.