The Nervous System Part 3- Neurotransmitters and Synaptic Integration Flashcards
Where is Acetylcholine excitatory and where is it inhibitory?
Excitatory for some neurons in the CNS, at somatic motor neurons at the neuromuscular junction, and at some autonomic nerve endings. ACh is also inhibitory for some autonomic nerve endings.
Name the two types of cholinergic receptors.
Nicotinic ACh receptors and Muscarinic ACh receptors.
Where are Nicotinic ACh receptors found?
In specific regions of the brain, in post synaptic autonomic ganglia, and in post synaptic membranes of skeletal muscle fibers.
What effect does the binding of Acetylcholine to nicotinic receptors ALWAYS have?
Always excitatory
Where are Muscarinic ACh receptors found?
Found in the plasma membrane of smooth muscle cells, cardiac muscle cells, and the cells of particular glands. As well as in parts of the brain.
The regulation of the cardiovascular system, digestive system, and others depend on the activation of which cholinergic receptor and where?
The activation of muscarinic ACh receptors by ACh released from autonomic axons.
Agonists, give an example for each cholinergic receptor.
Drugs that bind to and thereby ACTIVATE receptor proteins
ex: Muscarine, from a poisonous mushroom Amanita muscaria, is an agonist of muscarine ACh receptors.
ex: Nicotine from tobacco plants is an agonist for nicotinic ACh receptors.
Antagonists, give an example for each cholinergic receptor.
Drugs that bind with and thereby REDUCE the ACTIVITY of the receptor proteins.
ex: Atropine, a drug derived from Atropa belladonna, a member of the deadly nightshade family is an antagonist of muscarinic receptors.
ex: Alpha-bungarotoxin (from krait snake venom) and curare are both antagonists to nicotinic ACh receptors.
One way a lot of nerve blocks function is by preventing the breakdown of what?
Acetylcholine
Two types of chemically regulated channels
Ligand-Gated Channel
(ligand=neurotransmitter and receptor protein=ion channel)
and G-Protein Coupled Channels
(ligand=neurotransmitter and receptor protein=NOT the ion channel but a different membrane protein that indirectly affects the ion channel)
Ligand-Gated Channel
- When the neurotransmitter ligand binds to its membrane receptor, a central ion channel opens through the same receptor/channel protein.
- The receptor protein is also an ion cannel, two functions of the SAME protein.
Nicotinic ACh receptors and receptors for the neurotransmitters: Serotonin, GABA, and glycine all use what method of interaction with their target cell?
Ligand-Gated Channels
Explain how Nicotinic ACh receptors work as ligand-gated channels.
-The receptor has 5 polypeptide subunits and two of those contain ACh binding sites. When both sites bind with ACh the channel opens.
What happens after two Acetylcholine molecules bind with the receptor sites for Nicotinic ACh receptors?
The ion channels open permitting the simultaneous diffusion of Na+ into the cell and K+ out of the postsynaptic cell. The inward flow of Na+ predominates because of its steeper electrochemical gradient.
Produces– Depolarization of an excitatory postsynaptic potential (EPSP).
Because of the simultaneous diffusion of Na+ and K+ into and out of the cell when a Nicotinic ACh receptor has been activated the membrane polarity differs from that of an active potential how?
Na+ predominates in an EPSP but the simultaneous outward diffusion of K+ prevents the depolarization from overshooting 0 millivolts. So the membrane polarity does NOT reverse in an EPSP as it does in an action potential.
Where do action potentials occur?
In axons where voltage-gated channels are located.
Where do excitatory postsynaptic potentials occur?
In the dendrites and cell body.
Excitatory PostSynaptic Potentials are graded in magnitude, describe what this means and how it differs from action potentials.
EPSPs have no threshold. The ACh released from a single synaptic vesicile produces a tiny depolarization of the postsynaptic membrane. When more vesicles are stimulated to release ACh the depolarization is correspondingly greater. Action potentials on the other hand are an all or nothing event. EPSPs also have no refractory period and are capable of summation.
What is summation?
Summation- the depolarizations of several different EPSPs can be added together. (Action potentials cannot summate because of all or none nature and refractory periods)
Muscarinic ACh receptors, as well as the receptors for dopamine and norepinephrine, are what type of channel?
G-Protein-Coupled Channels
Explain how muscarinic ACh receptors function as G-Protein Coupled channels.
Muscarinic ACh receptors are formed from a single subunit, which binds to one ACh molecule while the rest of the receptor protein forms intracellular loops. Binding of ACh (the ligand) to the muscarinic receptor causes it to activate a complex of proteins in the cell membrane known as G-proteins, which then through a series of steps end up affecting the permeability of K+ channels.
Explain the details of what happens with G-Proteins in response to the binding of ACh to its receptor.
(like in Muscarinic ACh receptors)
Three G-protein subunits, Alpha, Beta, and Gamma.
- ACh binds to receptor, causing alpha subunit to dissociate from the other two subunits.
- Beta and Gamma now form a beta-gamma complex.
- Depending on the case either the alpha subunit or beta-gamma complex diffuses through the membrane until it binds to an ion channel.
- Binding causes the ion channel to open or close.
- Short time later the alpha subunit, or b-g complex dissociates from the channel and moves back to its previous position.
- That causes the ion channel to close or open.
Binding of ACh to muscarinic receptors indirectly affects the permeability of K+ channels. What affects happen to the cell if the K+ channel is opened or closed?
K+ Open=
K+ will rush out of the cell because it is the direction of its concentration gradient. That causes the cell to become HYPERPOLARIZED, which produces an inhibitory postsynaptic potential (IPSP).
K+ Closed=
K+ still diffuses out at an ongoing rate (K+ leakage channels) but because the channels are closed the outward diffusion of K+ is reduced to below resting potentials. The resting membrane potential is maintained by a balance between cations flowing in and out, so a reduction in the outward flow of K+ causes DEPOLARIZATION
Give an example of where ACh binds to muscarinic receptors and indirectly causes K+ channels to open.
In the heart muscle cells the beta-gamma complex binds to K+ channels and causes the channel to open. This leads to hyperpolarization, IPSPs, and an inhibition effect on the heart muscle cells and causes the heart rate to slow.
(Autonomic nerve fibers that are part of the vagus nerve synapse with pacemaker cells to slow the rate of the beat via this mechanism)
Who studied the vagus nerve and its slowing effect on the heart when it released “vagus stuff”?
Otto Lewi, and “vagusstuff” was referring to Acetylcholine.
Give an example of where ACh binds to muscarinic receptors and indirectly causes K+ channels to close.
When ACh binds to muscarinic receptors in the smooth cells of the stomach it causes alpha subunits to dissociate and bind to the K+ channel, closing the channel. This depolarization of the smooth muscle cells results in contractions of the stomach.
The ACh-receptor complex quickly dissociates, but will reform quickly as long as free ACh is in the vicinity. In order for activity in the postsynaptic cell to be stopped, free ACh must be inactivated very soon after it is released. What enzyme is responsible for this inactivation?
Acetylcholinesterase (AChE)
Acetylcholinesterase is present in only two places, where are they?
On the postsynaptic membrane, or immediately outside the membrane with its active sit facing the synaptic cleft.
How does acetylcholinesterase deactivate acetylcholine?
AChE binds to ACh and hydrolyzes the ACh into acetate and choline. The acetate and choline are then released into the synaptic cleft and reenter the PREsynaptic axon terminal and can be re-synthesized into ACh.
