GABA receptor: Difference between revisions

'''GABA''' (i.e. gamma-aminobutyric acid) is the primary inhibitory neurotransmitter of the vertebrate central nervous system (Kerr, 1995). GABA can bind one of two different receptor proteins, each using a discrete mechanism to elicit a cellular response. Upon binding with GABA, '''GABAB receptors''' utilize a second messenger amplification pathway that ultimately results in an inhibitory signal for neuronal transmission. This pathway for signal transmission differs from '''GABAA receptors''', which are considered ligand-gated ion channels as the binding of GABA results in the opening of ion channels leading to the inhibition of a neuronal signal. Excitatory neurosteroids have excitatory effects on neurotransmission. They act as potent negative allosteric modulators of the GABAA receptor. Major examples include the pregnanes pregnenolone sulfate (PS), epipregnanolone, and isopregnanolone (sepranolone).   

GABAB receptors have been found to provide an inhibitory function through coupling to G-proteins and the recruitment of second messengers (Bettler, 2004). Presynaptic GABAB receptors effectively repress the influx of calcium ions (Ca2+) via the inhibition of voltage gated Ca2+ channels through the activation of the Gβγ subunits (Bettler, 2004). Postsynaptic GABAB receptors then activate the opening of potassium ion (K+) channels through the activation of Gβγ subunits (Bettler, 2004). The efflux of potassium ions results in hyperpolarization of the neuronal membrane due to the highly negative Nernst value of potassium common to cerebrospinal fluid. Hyperpolarization of the neuronal membrane is the decrease in the neuron’s membrane potential away from threshold which results in the inhibition of GABA neuronal function (Bettler, 2004). This functions in opposition of the GABAA receptor in order to control and slow the inhibitory postsynaptic potentials as the GABAA receptor activation causes a more transient inhibitory signal (Cryan, 2005). Besides interacting with ion channels, GABAB receptors also inhibit adenylyl cyclase through the Giα/Goα subunits and activate adenylyl cyclase through Gβγ subunits (Bettler, 2004). This control of adenylyl cyclase is thought to control neuronal function for a longer period of time compared to the control via ion channels (Geng, 2013).