GABA Receptor Currents Research Articles

Cyclic AMP-dependent protein kinase decreases GABA A receptor current in mouse spinal neurons

GABA, the major inhibitory neurotransmitter in the mammalian brain, binds to GABA A receptors, which form chloride ion channels. The predicted structure of the GABA A receptor places a consensus phosphorylation site for cAMP-dependent protein kinase (PKA) on an intracellular domain of the channel. Phosphorylation by various protein kinases has been shown to alter the activity of certain ligand- and voltage-gated ion channels. We have examined the role of phosphorylation by the catalytic subunit of PKA in the regulation of GABA A receptor channel function using whole-cell and excised outside-out patch-clamp techniques. Inclusion of the catalytic subunit of PKA in the recording pipettes significantly reduced GABA-evoked whole-cell and single-channel chloride currents. Both heat inactivation of PKA and addition of the specific protein kinase inhibitor peptide prevented the reduction of GABA-evoked currents by PKA. Neither mean channel open time nor channel conductance was affected by PKA. The reduction in GABA receptor current by PKA was primarily due to a reduction in channel opening frequency.

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.