GABA-B receptor · Grey Matter

The GABA-B receptor is the slow, metabotropic receptor for GABA: through a G protein it opens potassium channels on the receiving cell and closes calcium channels on terminals, giving an inhibition that peaks after tens to hundreds of milliseconds and lasts for hundreds.

GABA-B receptor. The GABA-B receptor is the slow, metabotropic receptor for GABA: through a G protein it opens potassium channels on the receiving cell and closes calcium channels on terminals, giving an inhibition that peaks after tens to hundreds of milliseconds and lasts for hundreds.

The receptor is a pair of subunits (GABA-B1 and GABA-B2) coupled to G proteins of the inhibitory type. On the postsynaptic side the freed G-protein subunits open GIRK potassium channels; potassium leaves and the membrane hyperpolarises in a slow inhibitory potential that peaks at about 50 to 250 ms and decays over 100 to 500 ms. On presynaptic terminals the same receptors inhibit calcium channels and reduce release, both of GABA itself (as autoreceptors) and of glutamate (as heteroreceptors).

It needs a lot of GABA. GABA-B receptors sit mostly outside the synapse, so they respond when release is strong or synchronous enough for GABA to spill over, which makes them a gauge of intense inhibitory activity.

It shapes slow rhythms. The long hyperpolarisation it produces helps pace slow oscillations in the thalamus and cortex.

Baclofen, an agonist, relaxes spasticity by reducing release in the spinal cord.

GABA-A says stop now, GABA-B says stay quiet for a while.

The same transmitter gives two timescales of inhibition, depending on which receptor it reaches.

Questions: How do GABA-B receptors on a terminal reduce the transmitter it releases? Presynaptic GABA-B receptors activate G proteins whose freed subunits bind the terminal's voltage-gated calcium channels and make them harder to open. Because release rises with roughly the fourth power of calcium entry, a modest cut in calcium lowers the probability of release substantially. On GABA terminals this is autoinhibition, limiting how much GABA the next spikes release; on glutamate terminals, as heteroreceptors, it lets nearby inhibition turn down excitation. Baclofen, a GABA-B agonist, uses this effect in the spinal cord to reduce spasticity. Why does GABA produce both a fast and a slow inhibition? GABA acts on two different receptors. The GABA-A receptor is a chloride channel that opens within a millisecond, and its current decays over roughly 5 to 10 ms at fast synapses (longer at others). The GABA-B receptor is metabotropic: it acts through a G protein that opens GIRK potassium channels, so the inhibition peaks after about 50 to 250 ms and decays over 100 to 500 ms. GABA-B receptors sit mostly outside the synapse and need GABA to spill over, so they come into play when inhibitory cells fire strongly or together, adding a long tail of quiet after intense inhibition.