Receptors: Ionotropic and Metabotropic

The two great families of neurotransmitter receptor: fast ion-channel receptors that open in a millisecond, and slower G-protein-coupled receptors that trigger chemical cascades — and why the same transmitter can do opposite things.

A neurotransmitter has no meaning on its own. What it does depends on the receptor it binds. There are two main families.

Ionotropic receptors: fast

Ionotropic receptors are ion channels with a transmitter binding site built in. When transmitter binds, the channel opens within a millisecond or so and ions flow. Examples include the AMPA and NMDA receptors for glutamate (excitatory, letting in sodium and, for NMDA, calcium), the GABA-A receptor (inhibitory, letting in chloride), the glycine receptor, the nicotinic acetylcholine receptor at muscles, and the 5-HT3 serotonin receptor. They carry the brain's fast, point-to-point signals.

Metabotropic receptors: slow and versatile

Metabotropic receptors are not channels. Most are G-protein-coupled receptors (GPCRs), which snake through the membrane seven times. When transmitter binds, they activate a G protein inside the cell, which can open or close separate channels, or switch on enzymes producing second messengers such as cyclic AMP, which in turn activate protein kinases and can even alter gene expression. Effects begin within tens to hundreds of milliseconds and can last seconds, minutes or longer.

Examples include muscarinic acetylcholine receptors, all five dopamine receptors (D1–D5), most serotonin receptors, metabotropic glutamate receptors, GABA-B receptors, opioid receptors and cannabinoid receptors. GPCRs are the target of a large share of all prescription drugs.

One transmitter, many effects

Because there are many receptor subtypes, a single transmitter can do different — even opposite — things in different places. Acetylcholine contracts skeletal muscle through nicotinic receptors but slows the heart through muscarinic ones. Dopamine D1 receptors tend to excite their cells while D2 receptors tend to inhibit theirs.

The NMDA receptor: a coincidence detector

The NMDA receptor needs two things at once: glutamate bound, and the cell already depolarised, which pops a magnesium ion out of its pore. It therefore opens only when the sending and receiving neurons are active together — making it a molecular detector of the "fire together, wire together" rule behind learning.