Metabotropic receptor · Grey Matter

A metabotropic receptor is a receptor that, when its transmitter binds, sets off a chain of chemical reactions inside the cell instead of opening a pore itself, so its effects are slower (from tens of milliseconds to minutes), longer-lasting and more varied than those of an ion channel.

Metabotropic receptor. A metabotropic receptor is a receptor that, when its transmitter binds, sets off a chain of chemical reactions inside the cell instead of opening a pore itself, so its effects are slower (from tens of milliseconds to minutes), longer-lasting and more varied than those of an ion channel.

Almost all are G protein-coupled receptors. The bound receptor activates a G protein on the inner face of the membrane, which either acts directly on nearby channels (opening GIRK potassium channels, closing calcium channels) or switches on enzymes that make second messengers such as cyclic AMP or release calcium from internal stores. Those messengers activate kinases that change channels, receptors and even gene expression. Each step can amplify, so one bound receptor can affect many molecules.

Most neuromodulators act here. Dopamine, noradrenaline, serotonin (except at 5-HT3), histamine, neuropeptides and endocannabinoids work almost entirely through metabotropic receptors, as do the muscarinic receptors for acetylcholine and the GABA-B receptor.

Glutamate has them too. The metabotropic glutamate receptors (mGluRs) tune release and excitability and take part in some forms of long-term depression.

Their effects can outlast the transmitter. A cascade that phosphorylates a channel changes the cell until a phosphatase reverses it, which is why a brief neuromodulatory signal can reset a circuit for seconds or minutes.

An ionotropic receptor sends a message; a metabotropic receptor changes the receiver.

The first moves the voltage now, the second changes how the cell will respond to everything that follows.

Questions: Why do some receptors act in milliseconds and others over seconds or minutes? An ionotropic receptor is itself a channel, so binding opens the pore directly and current flows within a fraction of a millisecond; AMPA, NMDA, GABA-A, glycine and nicotinic receptors work this way. A metabotropic receptor has no pore: it activates a G protein, which then opens or closes separate channels or switches on enzymes that make second messengers, and each step adds time. Its effects start after tens to hundreds of milliseconds and can last seconds to minutes, because the messengers and the phosphorylations they cause outlive the transmitter. The two designs split the work: ionotropic receptors carry the content of signals, metabotropic ones adjust how cells respond to them.