Abstract
NH4Cl (10 mM) caused a sustained increase of the cell volume in immobilized, perfused F98 glioma cells to approx. 125 of control after 3 hours, as measured by diffusion-weighted 1H NMR spectroscopy. Concomitantly, the glutamine concentration increased by 130, accompanied by a marked decrease in cytosolic osmolytes, i.e. myo-inositol and taurine, determined from 1H NMR spectra of PCA extracts. Inhibition of glutamine synthetase partially prevented the increase in water content. While losses of organic osmolytes are also observed under hypotonic conditions, the rapid cell swelling is followed by the regulatory cell volume decrease (RVD), and is accompanied by decreased cytosolic glutamine. We suggest that the rise in intracellular osmolarity, which is attributed to NH4Cl metabolism to glutamine, but also to alanine, is not compensated by the release of other osmolytes, and causes cell swelling without RVD.
