Amobarbital inhibits K(+)-stimulated glucose oxidation in cerebellar granule neurons by two mechanisms.

The study aimed at determining mechanism(s) by which amobarbital (amytal) suppresses glucose oxidation in cerebellar granule neurons in primary cultures, a glutamatergic preparation. When challenged with a depolarizing K(+) concentration (55 mM), the cells doubled their rate of glucose oxidation (production of 14CO(2) from U-[14C]glucose) and glycolysis (lactate accumulation). At normal K(+) concentration, amobarbital reduced 14CO(2) production with half-maximum effect at 0.5-1 mM; at 55 mM K(+), the inhibition was more potent, with more than half of the K(+)-induced stimulation abolished at 50 microM. Dixon plot analysis showed a single inhibitory mechanism at 5.4 mM K(+), but at 55 mM K(+), two kinetically different mechanisms could be distinguished. A more pronounced compensatory amobarbital-induced increase in glycolysis at 5.4 than at 55 mM K(+) suggested that amobarbital in addition to its inhibition of mitochondrial respiration inhibited K(+)-induced increase in energy demand, probably by its known suppression of stimulated glutamate release.