Ionotropic receptor · Grey Matter

An ionotropic receptor is a receptor that is itself an ion channel: when the transmitter binds, the pore opens and ions flow at once, so it carries the fast signals of the brain, lasting milliseconds.

Ionotropic receptor. An ionotropic receptor is a receptor that is itself an ion channel: when the transmitter binds, the pore opens and ions flow at once, so it carries the fast signals of the brain, lasting milliseconds.

Binding and opening are one movement of the same protein, which is why the response begins within a fraction of a millisecond and ends soon after the transmitter leaves. The ions the pore lets through decide the sign of the signal. Channels for sodium and potassium (and sometimes calcium) excite: the AMPA and NMDA receptors for glutamate, the nicotinic receptors for acetylcholine and the 5-HT3 receptor for serotonin. Channels for chloride inhibit in the mature brain: the GABA-A receptor and the glycine receptor.

Speed differs within the family. An AMPA current decays in a few milliseconds, a GABA-A current in about 5 to 10 ms or more, an NMDA current over around 100 ms, because each stays open and lets go of its transmitter at its own rate.

Most are built from five subunits around a central pore (glutamate receptors from four), and the mix of subunits changes their speed and drug sensitivity, which is why the same receptor type behaves differently in different cells.

They are the targets of fast-acting drugs: benzodiazepines on GABA-A, ketamine in the NMDA pore, nicotine on nicotinic receptors, muscle relaxants on the nicotinic receptor of muscle.

An ionotropic receptor turns a molecule into a current with nothing in between.

That directness buys speed; the slower, amplified alternative is the metabotropic receptor.

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. How can acetylcholine act both in milliseconds and over seconds? It has two receptor families. Nicotinic receptors are ion channels, so acetylcholine opens them within a millisecond; at the neuromuscular junction this fires every muscle fibre the motor neuron reaches. Muscarinic receptors are coupled to G proteins, so their effects start more slowly and last seconds; in the cortex they mostly close potassium channels and make neurons more excitable. Acetylcholinesterase in the cleft ends the fast signal within about a millisecond, which keeps neuromuscular transmission sharp, while in the brain the slower muscarinic actions shape attention and arousal. Why does strychnine cause violent muscle spasms? In the spinal cord and brainstem, inhibitory interneurons release glycine onto motor neurons, opening glycine receptors (chloride channels) that keep the motor neurons from responding to every input and let opposing muscles relax in turn. Strychnine binds the glycine receptor at the glycine site and blocks it. With that inhibition gone, any sensory input (a touch, a sound) drives motor neurons unchecked, and whole groups of muscles contract together in painful spasms. The brain stays largely unaffected at first, since forebrain inhibition relies mostly on GABA, which is why consciousness is usually preserved.