Mechanisms of gentamicin-induced dysfunction of renal cortical mitochondria : II. Effects on mitochondrial monovalent cation transport

Abstract

Mitochondrial swelling techniques were used to evaluate the effects of the aminoglycoside antibiotic gentamicin on renal cortical mitochondrial monovalent cation permeability. Gentamicin behaved like EDTA to enhance energy-dependent Na+- and K+-acetate uptake with a relatively greater effect on Na+-acetate uptake. Mg2+ prevented and reversed the effects of both EDTA and gentamicin. Neither agent affected energy-independent uptake of Na+ and K+-acetate. Gentamicin did not enhance energy-independent uptake of K+- and Na+-nitrate. Gentamicin enhanced energy-dependent swelling in a chloride- and phosphate-containing medium as a function of the medium Na+ and K+ concentration. This effect occurred simultaneously with gentamicin-induced stimulation of State 4 respiration and was blocked by Mg2+. Gentamicin did not affect phosphate transport. The results are taken to indicate a specific action of gentamicin to enhance mitochondrial monovalent cation permeability at an Mg2+-sensitive site and it is proposed that this accounts for the effects of gentamicin on mitochondrial respiration.