Neurotransmitter receptors Domina Petric, MD

Ionotropic receptors I.

Nicotinic acetylcholine receptor It is occupied and activated by nicotine in smokers. Channel opening is gated by the binding of the neurotransmitter to its receptor.

Glutamate ionotropic receptors AMPA NMDA Kainate

NMDA receptors Both glutamate and glycine have to interact with the receptor to open the channel. Magnesium ions can aggregate in the deep binding site of the NMDA receptor. When the magnesium is bind there is no conductance.

GABA receptors There are places on the GABA receptors for: picrotoxin benzodiazepines barbiturates steroids Chloride ions pass through the channel from the inside to outside typically in mature neurons.

http://michaeldmann.net Ionotropic receptor

Calcium is critical for mediating synaptic plasticity. http://www.interactive-biology.com

Metabotropic receptors II.

G-protein coupled receptor Receptor is a monomeric integral membrane protein. It is associated with G proteins on its cytoplasmic surface. When the neurotransmitter binds to the receptor, G proteins become activated. G proteins interact with effector proteins. Effector proteins produce variety of intercellular messengers and those messengers can gate some ion channels.

G-protein coupled receptor Neurotransmitter binds Intercellular messengers gate ion channel Receptor Effector protein produces intercellular messengers G protein is activated and interacts with effector protein. Amplification of the signal

G-protein coupled receptor There can be amplification of the signal as these metabolic steps are occuring. G-protein coupled receptors can also interact with transcription factors that can modify gene expression. CREB binding domene in our genes is the regulatory element which can be activated with G-protein cuopled receptors. Transduction of photons into electrical energy requires the activation of G-protein coupled receptor system.

Synaptic integration III.

Synapse Action potential invades the end of an axon (presynaptic terminal). Wave of depolarisation conveys positive charge along the length of presynaptic terminal. When depolarisation reaches voltage gated calcium channels, channels open and there is influx of calcium. Calcium is the key trigger that leads to the fusion of docked vesicles. Neurotransmitter in docked and now fused vesicles passively diffuse out into the synaptic cleft.

Excitatory postsynaptic potential The reversal potential of the active conductance is above the threshold for firing an action potential.

Inhibitory postsynaptic potential For example if there is activation of GABA synapse, there will be hyperpolarisation due to chloride ions influx.

Excitatory activity of GABA in developing brain In the immature neuron there is more chloride ions inside of the cell than in mature neuron because of: Na+/K+/2 Cl- transporter (all ions go inside the cell) that will be replaced with K+/Cl- transporter (both ions go out of the cell) in mature neuron. So in the immature neuron there is high concentration of chloride ions INSIDE the cell and low concentration of chloride ions in the extracellular space. In immature neuron GABA is excitatory neurotransmitter. In mature neuron GABA is inhibitory neurotransmitter.

Another book association (Domina Petric, MD) Immature neuron Mature neuron When the child is born, ˝the book˝ opens and chloride ions escape from the cell to the exctracellular space because of the new transporter that throws out of the cell chloride ions. Immature neuron is like closed book with chloride ions inside the book (inside the cell). GABA is excitatory neurotransmitter. GABA is inhibitory neurotransmitter. When the channel opens, chloride ions When the channel opens there will be go out of the cell and there is influx of chloride ions from extracellular space depolarisation. into the cell (hyperpolarisation).

Synapse integration No one synapse is strong enough to result in the generation of an action potential in the postsynaptic neuron. There must be many synapses, many excitatory inputs converging on the same neuron at the same time in order to depolarize that membrane sufficiently to reach treshold.

Literature https://www.coursera.org/learn/ medical-neuroscience/lecture: Leonard E. White, PhD, Duke University http://michaeldmann.net http://www.interactive-biology.com