Pentobarbital and picrotoxin have reciprocal actions on single GABAA receptor channels

Pentobarbital (PB) and picrotoxin (PIC) bind to allosterically coupled sites on the GABAA receptor complex but have opposite effects on GABA receptor currents. PB, an anesthetic/anticonvulsant, enhances, and PIC, a convulsant, inhibits GABA receptor currents. PB and PIC also had opposite effects on single main conductance channel GABA receptor currents recorded from excised outside-out patches from mouse spinal neurons in culture. PB prolonged bursts of channel openings by increasing mean duration and number of intraburst openings. PIC shortened bursts by reducing mean duration and number of intraburst openings. The results demonstrate the reciprocal regulation of GABA receptor channels by PB and PIC and suggest that their allosterically coupled binding sites are coupled to the chloride channel in an opposite manner.