Mechanism of extracellular potassium stimulation of protein synthesis in the in vitro hippocampus.

Abstract

AbstractTransverse slices of guinea‐pig hippocampus respond to small increases in extracellular potassium concentration [K +] by showing a marked augmentation in the rate of incorporation of labelled precursor amino acid into protein. We find that this augmentation is manifested equally in superfusing solutions containing low specific activity/high concentration precursor and high specific activity/low concentration precursor. This provides additional evidence that the effect of extracellular [K +] is on the rate of protein synthesis and not on the precursor pool. Extracellular [K +] augments amino acid incorporation normally in the presence of concentrations of α‐amanatin and actinomycin D which are inhibiting RNA synthesis by over 97%. This suggests the effect is exerted post‐transcriptionally. Extracellular [K +] causes an unattenuated increase in protein synthesis in the presence of high Mg2+ (20mm) or low Ca2+ (0 mm) in the superfusate–suggesting this effect of [K +] does not result from an effect on neurotransmitter release. Increases in extracellular [K+] which increase protein synthesis threefold (1.3‐6.4mm‐K +) increase the intracellular [K +]/[Na +] 2‐fold. 3 x 10‐7m‐Ouabain. which lowers incorporation by 40‐50% lowers [K +]/[Na +] by about 50% while having no effect on the uptake of labelled precursor or on the cell concentrations of ATP. These results suggest that protein synthesis in the cell is sensitive to [K. +]/[Na +] and that an alteration in this ratio is the mechanism by which the concentration of extracellular [K +] affects the rate of in vitro hippocampal protein synthesis. This effect of extracellular [K +] on synthesis is not observed in slices from non‐cerebral organs of the guinea pig.