User:Bizzers03/Glycine receptor

History

Glycine and its receptor were first suggested to play a role in inhibition of cells in 1965. Two years later, experiments showed that glycine had a hyperpolarizing effect on spinal motor neurons due to increased chloride conductance through the receptor. Then, in 1971, glycine was found to be localized in the spinal cord using autoradiography. All of these discoveries resulted in the conclusion that glycine is a primary inhibitory neurotransmitter of the spinal cord that works via its receptor.

Structure

(a): shows three agonists and one antagonist of the glycine receptor. (b): the fetal form of the receptor is made up of five α2 subunits, while the adult form is made up of both α1 and β subunits.

The embryo form on the other hand, is made up of five α2 subunits.

Function

Adults

In mature adults, glycine is a inhibitory neurotransmitter found in the spinal cord and regions of the brain. As it binds to a glycine receptor, a conformational change is induced, and the channel created by the receptor opens. As the channel opens, chloride ions are able to flow into the cell which results in hyperpolarization. In addition to this hyperpolarization which decreases the likelihood of action potential propagation, glycine is also responsible for decreasing the transmission of both inhibitory and excitatory neurotransmitters as it binds to its receptor. This is called the "shunting" effect and can be explained by Ohm's Law. As the receptor is activated, the membrane conductance is increased and the membrane resistance is decreased. According to Ohm's Law, as resistance decreases, so does voltage. A decreased postsynaptic voltage results in a decreased transmission of neurotransmitters.

Embryos

In developing embryos, glycine has the opposite effect as it does in adults. It is an excitatory neurotransmitter. This is due to the fact that chloride has a more positive equilibrium potential in early stages of life due to the high expression of the Na+-K+-Cl- cotransporter 1 (NKCC1). This moves one sodium, one potassium and two chloride ions into the cell, resulting in a higher intracellular chloride concentration. When glycine binds to its receptor, the result is an efflux of chloride, instead of an influx as it happens in mature adults. The efflux of chloride causes the membrane potential to become more positive, or depolarized. As the cells mature, the K+-Cl- cotransporter 2 (KCC2) is expressed, which moves potassium and chloride out of the cell, decreasing the intracellular chloride concentration. This allows the receptor to switch to an inhibitory mechanism as described above for adults.