INHIBITION OF NA-ATPASE FROM RAT-BRAIN CORTEX BY PROPIONIC-ACID(,K+)

BUFFERED propionic acid was injected s.c. into rats twice a day at 8 h intervals from the 6 to 21 days of age. Control rats received saline in the same volumes. The animals were weighed and killed by decapitati on at 23 days. Whole brain and cerebral cortex were weighed and synapt ic plasma membranes were prepared from cortex for the determination of Na+,K+-ATPase and Mg2+-ATPase activities. Body, whole brain and corti cal weights were similar in the two groups, suggesting that propionic acid does not cause malnutrition in rats. Na+,K+-ATPase activity was s ignificantly reduced by 30% in membranes from the propionate-treated g roup, whereas Mg2+-ATPase activity was not. In another set of experime nts, synaptic plasma membranes were prepared from cerebral cortex of 2 3-day-old rats and incubated with propionic acid at final concentratio ns ranging from 0.1 to 2.0 mM. Na+,K+-ATPase activity, but not Mg2+-AT Pase activity, was inhibited by 22-32%. Since propionic acid concentra tions in plasma of chronically treated rats and of propionic acidaemic children are of the same order of magnitude as those tested in vitro, the results suggest that the inhibition of Na+,K(+)ATPase activity ma y be related to the neurological dysfunction of patients affected by p ropionic acidaemia. (C) 1998 Rapid Science Ltd.