Phenobarbital actions in vivo: effects on extra cellular potassium activity and oxidative metabolism in cat cerebral cortex.
Extracellular potassium 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 potassium. Phenobarbital (i.v.) produced, within minutes, a persistent shift in NAD to a more reduced level indicative of decreased oxygen consumption. Electrical excitability of the cortex also decreased within minutes, although there was no concomitant change in the resting extracellular potassium activity. Cortical stimulation produced transient elevations of [K+]0 and NADH oxidation and these responses returned to base lines more slowly following the barbiturate administration. However, the proportionality between NADH oxidation and [K+]0 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 oxygen consumption was decreased. The prolongation of recovery metabolism following phenobarbital was interpreted as being the result of protracted elevation of extracellular potassium activity. The slow return to "resting" levels of extracellular potassium is probably caused by interference with passive clearance mechanisms.
D000818:Animals; D002415:Cats; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D003580:Cytochromes / Q000378:metabolism; D004558:Electric Stimulation; D004579:Electron Transport; D005110:Extracellular Space / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D008297:Male; D009243:NAD / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects*; D010634:Phenobarbital / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism*
D003580:Cytochromes; D009243:NAD; D011188:Potassium; D010634:Phenobarbital