Neurotransmitters and Receptors Flashcards
How are neurotransmitters removed from the synaptic cleft?
Diffusion, reuptake, or degradation
What are the criteria for neurotransmitters?
They must be present in the presynaptic neuron.
They must be released in response to presynaptic depolarization, and this release is dependent on calcium influx into the presynaptic terminal.
Specific receptors must be present on the postsynaptic cell.
Ligand-gated ion channels
They are directly linked to an ion channel. They have two functional domains: an extracellular site that binds neurotransmitters and a membrane-spanning domain that forms the selective ion channel. Also known as ionotropic receptors.
Made up of four or five individual protein subunits, each of which contributes to the pore of the ion channel.
Combines transmitter binding and channel functions in a single structure
G-protein coupled receptors
The eventual movement of ions through a channel depends on multiple metabolic steps. The receptor and ion channel are physically separate and the channel is activated by G proteins.
Also called metabotropic receptors
Monomeric protein receptor with extracellular domain that contains transmitter binding site and intracellular domain that binds to G-proteins. G-proteins dissociate from the receptor and interact with the ion channel.
Nicotinic acetylcholine receptor
A ligand-gated ion channel (ionotropic receptor) consisting of five subunits arranged symmetrically around a central pore. Each subunit has a long, hydrophilic N-terminal domain, Three hydrophobic segments (membrane-spanning), A stretch of hydrophilic domain, and a fourth hydrophobic membrane spanning domain segment near the C-terminus
Where is the acetylcholine binding site on the nicotinic acetylcholine receptor?
it is thought to be near the two consecutive cysteines found in the N-terminal domain (extracellularly)
What part of the nictonic acetylcholine receptor subunits lines the ion channel/pore?
The second transmembrane segment (TM2)
What causes the ion channel in nACh receptors to open? (What is the actual mechanism)
When acetylcholine binds, the TM2 segments rotate 90 degrees. The TM2 segments are alpha-helices with a kink in their center.
Where is acetylcholine used as a neurotransmitter?
Skeletal muscle motoneurons, presynaptic cells of the autonomic nervous system and postsynaptic cells of the parasympathetic nervous system
Formation of acetylcholine
Acetyl-CoA and choline are combined by choline acetyltransferase
What happens to acetylcholine after it is released into the synaptic cleft?
It binds to ligand-gated channels on the post-synaptic membrane for about 1 millisecond, then it is broken down to choline (and acetate) by acetylcholinesterase in the synaptic cleft. Choline is taken up by sodium coupled choline transport in the presynaptic membrane and converted to acetylcholine by choline acetyltransferase. (Acetyl-CoA and choline are combined)
Nearly all ___ are glutamatergic.
excitatory neurons in the CNS
Glutamate receptors are one of these two types:
ionotropic and metabotropic
Subtypes of ionotropic glutamate receptors
AMPA and NMDA. AMPA channels are permeable to sodium and potassium and require only the presence of glutamate. NMDA channels are permeable to sodium, potassium, and calcium and require the presence of glutamate as well as partial membrane depolarization in order to open. NMDA is blocked by magnesium ions in the resting state.
AMPA channels
ionotropic glutamate receptors that are permeable to sodium and potassium
NMDA Channels
Permeable to sodium, potassium, and calcium. Require the presence of glutamate as well as partial membrane depolarization in order to open. They are blocked by extracellular magnesium ions, which are removed by membrane depolarization. Calcium enters the cell and activates calcium dependent second messenger cascades.
Basis for long-term synaptic modifications important in learning and memory.
Subunits of glutamate receptors
Five subunits. TM2 does not completely traverse membrane. (Called pore loop)
Have four transmembrane parts
What happens to glutamate when it is released from synaptic vesicles?
Glial cells take it up and convert it into glutamine and cycle it back to the presynaptic cell (which converts it to glutamate)
Major inhibitory neurotransmitters
GABA and glycine
GABA stands for
gamma-aminobutyric acid
GABA receptors
five subunits with four transmembrane areas. GABA-A is an ionotropic chloride channel. GABA-B is a metabotropic potassium channel
Glycine receptors
Less prominent than GABA receptors. Used by inhibitory interneurons in spinal cord. Ionotropic glycine gated chloride channel.
Examples of G-protein coupled receptors
alpha and beta adrenergic receptors (epinephrine and norepinephrine), GABA-B receptors, metabotropic glutamate receptors, serotonin receptors, neuropeptide receptors, odorant receptors, and certain taste receptors.
Structure of G-protein coupled receptors
One peptide with seven transmembrane segments with a transmitter binding site on the extracellular surface and a G protein binding site on the intracellular face
Mechanisms by which a G protein mediated signaling cascade can open or close an ion channel
Transmitter binding alters receptor information, exposing a binding site for G-protein complex.
Diffusion of the G-protein in the bilayer leads to association of transmitter-receptor complex with G-protein complex, activating it for the GTP-GDP exchange.
Displacement of GDP for GTP causes the alpha subunit to dissociate from the G protein complex, exposing an active site which binds to the channel and opening it
Transmitter binding alters receptor information, exposing a binding site for G-protein complex.
Diffusion of the G-protein in the lipid bilayer leads to association of transmitter-receptor complex, activating it for the GTP-GDP exchange.
Displacement of GDP for GTP causes the alpha subunit to dissociate from the G-protein complex, exposing an active site which binds to adenylyl cyclase.
Binding of the alpha subunit to adenylyl cyclase results in release of many molecules of cAMP.
cAMP activates protein kinase to phosphorylate the channel, opening it.
What are the advantages and disadvantages of metabotropic receptors?
They are slower, but they can amplify signals and last longer (via protein phosphorylation).
