My close encounter with GABA B receptors

Abstract

In this review, I summarize the sequence of events involved in characterizing the functional role of GABA B receptors in the CNS and their involvement in synaptic transmission. The story was launched with the realization that baclofen was a selective agonist of GABA B receptors. This lead to the discovery in the CNS that GABA B receptor activation could result in a presynaptic inhibition of transmitter release as well as a postsynaptic increase in potassium conductance. Based on this information, it was found that GABA also activated a potassium conductance. A role for GABA B receptors in synaptic transmission was suggested by the fact that activation of GABAergic interneurons could generate a slow IPSP mediated by an increase in potassium conductance. To link this slow IPSP to GABA B receptors required a selective GABA B antagonist. Phaclofen was the first antagonist developed and was found to antagonize the action of baclofen and the GABA A independent action of GABA. Most importantly, it blocked the slow IPSP. The properties of GABA A and GABA B IPSPs are remarkably different. GABA A IPSPs powerfully inhibit neurons and rapidly curtail excitatory inputs. This greatly enhances the precision of excitatory synaptic transmission. GABA B IPSPs are recruited with repetitive and synchronous activity and are postulated to modulate the rhythmic network activity of cortical tissue.