Week 3 Flashcards
describe the structure of a chemical synapse. What is on either side of the synapse, how big is a synapse, what maintains the distance
The presynaptic cell ends with terminal boutons then there is a space between this and the postsynaptic cell. The space between is called the synaptic cleft and is very narrow (10 nm) so that neurotransmitter molecules are released very close to receptors. The physical association of the pre and postsynaptic cells is maintained by Cell Adhesion Molecules (CAMs) which are proteins that project from the cell membranes and bond in the cleft.
Describe the release of a neurotransmitter. What triggers release, how are they released
Release is triggered by action potentials that stimulate the entry of Ca2+ into the axon terminal through voltage gated Ca2+ channels. The neurotransmitters are contained in membrane bound synaptic vesicles which exocytize (exocytosis idk what word I want there) at the membrane, releasing the contents as the membranes fuse
What are the steps in the process of a synaptic vesicle fusing with the plasma membrane
- Docking happens before an action potential arrives:
SNARE proteins include one in the vesicle membrane (synaptobrevin-2) and two anchored in the plasma membrane (syntaxin and SNAP-25). They form a SNARE complex and bridge the two structures - Action potential arrives and Ca2+ enters the cytoplasm. A sensor protein called synaptotagmin (located on the synaptic vessicle) interacts with the SNARE complex and leads to fusion
What is another name for a neurotransmitter as it binds a receptor?
Ligand. A ligand is a small molecule that binds to and forms a complex with a larger protein molecule.
What type of receptor is associated with neurotransmitters?
Chemically regulated or ligand regulated (gated ion channels) which open in response to the binding of a ligand, in this case the neurotransmitter
Compare voltage and chemically regulated ion channels
Voltage: found primarily in the axons. open in response to depolarization
Chemical: found in the postsynaptic membrane. open in response to the binding of a postsynaptic receptor protein to its neurotransmitter ligand
Explain the types of potentials produced by chemically regulated ion channels
Opening of chemically regulated channels produces a graded potential. There are two types of graded potentials, either a depolarization or a hyperpolarization
Excitatory Postsynaptic potential (ESPS): depolarization event moves membrane potential toward the threshold required for an action potential (e.g. influx of Na+ or Ca2+)
Inhibitory Postsynaptic potential (ISPS): hyperpolarization event moves membrane potential farther away from the threshold for an action potential (e.g. influx of Cl-)
How are synaptic potentials (graded potentials) conducted to the axon? What does this indicate about signal strength?
EPSPs and IPSPs are produced at the dendrites and must propagate to the initial segment of the axon to influence acton potential production. They are conducted by cable properties only! This means that they decrease in amplitude as they move along dendrites to the cell body and axon.
describe the features of the axon initial segment
it is unmyelinated and has a high concentration of Na+ and K+ channels. This is the region where the action potential is first produced and serves as the site of synaptic integration (summation of IPSPs and EPSPs)
*Types of cholinergic receptors
Nicotinic ACh receptors: ALWAYS EXCITATORY. located on skeletal muscles, autonomic ganglia, and specific brain regions. stimulates muscle contraction. named because nicotine is an agonist as well for this receptor
Muscarinic ACh receptors: Can be excitatory or inhibitory because they are G protein coupled. Located on smooth muscle cells, cardiac muscle cells, brain, and particular glands. Required for cardiovascular system and digestive system. Named because muscarine (drug from shrooms) is an agonist
What are drugs called that activate receptor proteins? Examples? Drugs that inactivate and examples?
Agonists. Muscarine is an agonist of the muscarinic receptors. Nicotine is an agonist of the nicotinic receptors
Antagonists. Atropine is an antagonist of muscarinic receptors. Curare and a-bungarotoxin (krait snake venom) are antagonists of nicotinic receptors
What are ligand gated channels? (not the same thing as ligand regulated!) Give an example
Ligand gated channels are when the receptor protein is also an ion channel that opens and closes in response to the ligand binding. The one protein has two functions as a receptor and a channel.
Nicotinic ACh receptors are ligand gated channels. It binds 2 ACh and opens to permit simultaneous diffusion of Na+ and K+ into and out of the cell. The flow of Na+ is the dominant effect because of its steeper gradient. This produces a depolarization and an Excitatory Postsynaptic potential.
Compare action potentials and Excitatory Postsynaptic potentials
Action potentials: occur in the axons where voltage gated channels are located. Have a threshold requirement to produce the potential. Potential does not summate, has a refractory period, and is all-or-none.
EPSPs: occur in postsynaptic membrane of dendrites and cell body. They have no threshold and are graded in magnitude (more impulses = greater depolarization) and have no refractory period so are capable of summation (depolarizations of several different EPSPs can be added together)
What other type of chemically regulated channel exists besides ligand gated? Give an example of this type of receptor
G protein coupled channels. These consist of different, separate membrane proteins. Neurotransmitters indirectly opens ion channels via a G protein signal
The Muscarine ACh receptors are an example. The receptor is a single subunit which binds one ACh molecule and activates a G-protein complex. The alpha separates from beta-gamma and they migrate through the membrane and interact differently depending on the specific case and may open or close channels.
How does ACh effect the heart
ACh interacts with Muscarinic receptors which activate G-protein to dissociate. Beta-gamma binds K+ channels in heart muscle cells, cause to open = K+ leaves cell = hyperpolarized = IPSP. Vagus nerve (a parasympathetic nerve) does this when synapsing with pacemaker cells, slowing heart beat!
How does ACh effect the smooth muscle of the stomach
ACh binds muscarinic receptors and causes G-protein to activate and dissociate. Alpha subunits bind K+ channels and causes them to close. outward diffusion of K+ is reduced = depolarized = EPSP = contractions of the stomach
What removes acetylcholine from the synapse and how?
ACh and receptor dissociate quickly but will reform quickly if free ACh is present. In order to stop activity, the free ACh is inactivated by Acetylcholinesterase which is present on the postsynaptic membrane. AchE hydrolyzes the acetylcholine into acetate and choline which can then reenter the presynaptic cell and resynghesize ACh
How does Acetylcholine affect the skeletal muscle cells
The synapses (neuromuscular junctions) are at the postsynaptic membrane of the muscle fiber, known as the muscle end plate. So EPSPs are called end-plate potentials here. Only nicotinic receptors are located in muscle cells so all potentials are excitatory. Voltage gated channels open in response to the depolarization produced by ACh and the action potentials are reproduced along voltage gated channels down the sarcolemma (muscle membrane). This is analogous to axon action potential conduction. The result is muscle contraction
What is a drug that competes with ACh for attachment to the nicotinic receptors and what is the effect of the drug?
Curare is an antagonist for nicotinic ACh receptors and so reduces the size of the end-plate potentials in the muscles. Produces flaccid paralysis and death because diaphragm stops working. Used as a muscle relaxant in surgery and in electroconvulsive shock therapy to prevent muscle damage. Can also be used to counteract the effects of tetanus which contracts the muscles.
Explain the effect of ACh on the two classes of autonomic motor neurons
Sympathetic: ????
Parasympathetic: most of these neurons innervate the effector organs via ACh as their neurotransmitter. In some cases there is an inhibitory effect through binding of ACh to muscarinic receptors (such as the vagus nerve slowing heart beat). Other cases ACh can be excitatory like via nicotinic receptors.
What is the normal stimuli for the production of action potentials?
Excitatory postsynaptic potentials conducted from the dendrites and cell body.
The dendrites and cell body serve as the receptive area where receptor proteins for neurotransmitters and ligand gated channels are located. Graded, local EPSPs and IPSPs spread into the initial segment of the axon located by the axon hillock. If the EPSP depolarization is at or above threshold at the initial segment, an action potential will occur. A stronger EPSP will determine the frequency at which action potentials are produced. The action potential travels down the axon without loss of amplitude and ends at the terminal boutons of the axon where neurotransmitter is released.
Define monoamines and give some examples and what they are derived from
Monoamines are regulatory molecules derived from amino acids.
Dopamine, norepinephrine (noradrenaline), epinephrine (adrenalin) are derived from tyrosine and are a subfamily of monoamines called catecholamines.
Serotonin is derived from tryptophan
Histamine is derived from histidine
*What monoamine related medication is associated with drowsiness and why?
Histamine promotes wakefulness and alertness, so antihistamines for allergies can promote drowsiness
Where is norepinephrine and epinephrine secreted from? What family of monoamines are these neurotransmitters part of?
Secreted from the adrenal medulla
Part of the catecholamines