# Structural Biochemistry/Membrane Proteins/Ligand-gated Ion Channels
## Ligand-gated Ion Channels

Ligand-gated Ion Channels (LGICs) are a group of transmembrane ion channels that open when a signal molecule (ligand) binds to an extracellular receptor region of the channel protein. This binding changes the structural arrangements of the channel protein, which then causes the channels to open or close in response to the binding of a chemical messenger such as a neurotransmitter. This ligand-gated ion channel, a type of ionotropic receptor, allows specific ions (like Na+, K+, Ca2+, or Cl-) to flow in and out of the membrane. Examples of ligand-gated ion channels include acetylcholine receptors, serotonin receptor, GABA$_A$, and Glutamate receptor. http://commons.wikimedia.org/wiki/File:Ligand-gated_ion_channel.JPG

## Example
### External Ligands

3 superfamilies of extraceullarly activated ligand-gated ion channel subunits:
* Receptors of the cys-loop superfamily - five protein subunits which form a pentameric arrangement around a central pore
** Serotonin (5-HT) receptors are found in the central and peripheral nervous system. They mediate both excitatory and inhibitory neurotransmission and are activated by serotonin. They modulate the release of many neurotransmitters, including epinephrine, acetylcholine, and many hormones. Because of its wide versatility, the serotonin receptors influence many biological processes such as aggression, anxiety, appetite, cognition, learning, memory, mood, nausea, sleep, and thermoregulation. As one can see, this is one very important receptor.
** Glycine receptors is the receptor for neurotransmitter glycine. It is one of the most widely distributed inhibitory receptors in the central nervous system and has important roles in mediating inhibitory neurotransmission in the spinal cord and brain stem.
** Nicotinic Acetylcholine receptors are cholinergic receptors that form ligand-gated ion channels in the plasma membranes of specific neurons. At neuromuscular junctions, nicotinic acetylcholine receptors form a cation channel that opens when two molecules of acetylcholine bind to the channel's extracellular region. This results in sodium ion influx, which causes depolarization of the muscle cell membrane.
** GABA$_A$ receptor (GABA$_A$R) is an ionotropic receptor and ligand-gated ion channel. GABA$_A$ receptor is the binding site for GABA and several drugs such as muscimol, gaboxadol, and bicuculline. GABA$_A$ receptor allows Cl- to pass through its pore which hyperpolarizes the neuron. This inhibits neurotransmission by diminishing the chance of a successful action potential occurring.
* ATP-gated channel superfamily
* glutamate activated cationic channel superfamily
** NMDA receptor is a glutamate receptor that, when activated, triggers the opening of ion channels that creates a flux of calcium into the cell. It is both ligand-gated and voltage-gated, and its activation requires both glutamate and glycine. Calcium influx is thought to control synaptic plasticity and memory function, so NMDA receptor is a topic of interest for those who wish to learn about memory formation.
** AMPA receptor is an ionotropic transmembrane receptor for glutamate. It mediates fast synaptic transmission in the central nervous system. Native AMPA receptor channels are impermeable to calcium, a function controlled by the GluR2 subunit in the receptor. The calcium permeability is determined by the post-transcriptional editing of the GluR2 mRNA. AMPA receptor permeabiilty to calcium determine largely the function of the signal transduction behavior.
** kainate receptors are ionotropic receptors that respond to glutamate. They are less well understood than AMPA and NMDA receptors. Kainate receptors are involved in excitatory neurotransmission via the activation of postsynaptic receptors, and they also participate in inhibitory neurotransmission by modulating release of GABA through a presynaptic mechanism.

### Internal Ligands

* "second messengers" cyclic AMP (cAMP)and cyclic GMP (cGMP)