PHENOBARBITAL ACTIONS INVIVO - EFFECTS ON EXTRACELLULAR POTASSIUM ACTIVITY AND OXIDATIVE-METABOLISM IN CAT CEREBRAL-CORTEX

Abstract

Extracellular K+ activity and changes in the reduction levels of intramitochondrial pyridine nucleotide (NAD) and cytochrome-a,a3 were monitored in the cerebral cortex of cats at rest and during electrical stimulation, before and after administration of sodium phenobarbital. Stimulation of the cortical surface evoked a transient increase in the level of oxidized NAD which was proportional in magnitude to the associated transient elevation of extracellular K+. Phenobarbital (i.v.) produced, within minutes, a persistent shift in NAD to a more reduced level indicative of decreased O2 consumption. Electrical excitability of the cortex also decreased within minutes, although there was no concomitant change in the resting extracellular K+ activity. Cortical stimulation produced transient elevations of [K+]o and NADH oxidation and these reponses returned to base lines more slowly following the barbiturate administration. The proportionality between NADH oxidation and [K+]o elevation was not altered by phenobarbital. The kinetics of the cytochrome-a,a3 response to cortical stimulation mirrored those of NADH, implying that phenobarbital was not blocking electron transport in the respiratory chain between NADH and cytochrome-a,a3 even at doses where resting tissue O2 consumption was decreased. The prolongation of recovery metabolism following phenobarbital was the result of protracted elevation of extracellular K+ activity. The slow return to resting levels of extracellular K+ was probably caused by interference with passive clearance mechanisms.