Synaptic Transmission Neurotransmitters and Receptors Flashcards
3 components of a synapse
- presynaptic terminal
- synaptic cleft
- postsynaptic terminal
Describe the series of events at an active chemical synapse (6 steps)
1) an action potential arrives at the presynaptic terminal
2) the change in electrical potential causes the opening of voltage-gated Ca2+ channels and the influx of calcium
3) elevated levels of Ca2+ then promote the movement of synaptic vesicles to the membrane
4) the synaptic vesicles bind with the membrane, then release NT into the synaptic cleft
5) NT diffuses across the synaptic cleft and activates a membrane receptor
6) the receptor associated with an ion channel opens when the receptor site is bound by NT, allowing positively charged ions to enter the postsynaptic cell
What is the significance of calcium in vesicle fusion?
The influx of Ca2+ is necessary and sufficient for vesicle fusion and neurotransmitter release
What are the 3 types of synapses?
- axosomatic (neuron - cell body)
- axodendritic (neuron - dendrite)
- axoaxonic (neuron - axon)
If the synapse is neuromuscular, axosomatic, or axodendritic, the flux of ions in the postsynaptic membrane generates what?
a local postsynaptic potential
What are postsynaptic potentials?
local changes in ion concentration across the postsynaptic membrane
When ion channels open on the postsynaptic membrane, due to NT binding, causes a local depolarization occurs it is said to be an _____ postsynaptic potential
excitatory postsynaptic potential (EPSP)
When ion channels open on the postsynaptic membrane, due to NT binding, causes a local hyperpolarization occurs it is said to be an _____ postsynaptic potential
inhibitory postsynaptic potential (IPSP)
An EPSP occurs when NT bind to postsynaptic membrane receptors that open ions channels, allowing the influx of what ions?
Na+ and Ca2+
The summation of EPSPs can lead to what?
The generation of an action potential
Describe an example of an excitatory postsynaptic potential
At the neuromuscular junction the binding of ACh is excitatory, which opens ligand-gated channels that allow Na+ influx into the muscle cell, initiating the mechanical contraction of the muscle cell
What is an IPSP?
a local hyperpolarization of the postsynaptic membrane, which decreases the possibility of an action potential
An IPSP involves a local flow of what ions in response to a NT binding to postsynaptic membrane receptors?
Cl- into the cell and/or K+ out of the cell (causing the cell to become more negative)
What are the 2 types of summation?
Spatial and Temporal
When action potentials arrive from different locations across the cell body simultaneously, it is called _____ summation
spatial
When action potentials do not arrive at the cell body simultaneously but their potentials overlap it is called _____ summation
temporal
Presynaptic _____ allows for more neurotransmitter to be released.
Presynaptic _____ allows for less neurotransmitter to be released.
facilitation
inhibition
When does presynaptic facilitation occur?
When a presynaptic axon releases a neurotransmitter that slightly depolarizes the axon terminal of a second neuron, which causes more Ca2+ than normal to enter the presynaptic neuron, causing more transmitter to be released to cleft resulting in increased stimulation of the postsynaptic neuron
When does presynaptic inhibition occur?
When an axon releases a neurotransmitter that slightly hyperpolarizes the axonal region of a second neuron which results in decreased stimulation of the postsynaptic cell membrane
How can one’s pain experience be intensified?
When someone mentally focuses on pain it can increase the level of activity of brain areas associated with the pain
A neuro____ is a chemical released by a presynaptic neuron into the synaptic cleft and acts directly on postsynaptic ion channels or activates proteins inside the postsynaptic neuron
neurotransmitter
A neuro____ is a chemical released into ECF and adjusts the activity of many neurons by altering neural function by acting at a distance away from the synaptic cleft
neuromodulator
Neuro_____ effects manifest more slowly and usually last a long time
Neuromodulator
Neuro_____ effects happen in seconds and last from minutes to days
Neurotransmitter
What are the 2 types of receptors on postsynaptic neurons that respond to NTs?
- ionotropic (direct)
- metabotropic (indirect)
Describe ionotropic receptors
NTs may affect the postsynaptic neuron directly, by activating ion channels (ionotropic)
Describe metabotropic receptors
NTs may affect the postsynaptic neuron indirectly, by activating proteins inside the postsynaptic neuron
NTs that act directly (on ionotropic receptors) are classified as what?
fast-acting
NTs that act indirectly (on metabotropic receptors) are classified as what?
slow-acting
Fast-acting neurotransmitter transmission requires how long?
less than 1/1000 of a second
Slow-acting neurotransmitter transmission requires how long?
1/10 of a second to minutes
How do slow-acting NTs regulate fast synaptic transmission?
By controlling the amount of NT released from the presynaptic terminals
What neurotransmitter is the major conveyor of information in the peripheral nervous system?
ACh
ACh is seen in what types of neurons?
All neurons that synapse with skeletal muscle fibers to elicit fast-acting effects on muscle membranes
Is ACh excitatory or inhibitory?
excitatory
What are ACh’s slow acting effects?
In the peripheral nervous system that regulate HR and other autonomic functions
What are 3 amino acid transmitters?
- Glutamate
- Glycine
- GABA
Which of the amino acid transmitters are excitatory and which are inhibitory?
Glutamate is excitatory. Glycine and GABA are inhibitory
Glutamate elicits changes that occur with what?
learning and development
Glycine is the major inhibitory transmitter where?
Postsynaptic membranes in the brainstem and spinal cord
GABA is the major inhibitory transmitter where?
CNS (particularly at interneurons within the spinal cord)
Inhibitory effects produced by glycine and GABA prevent what?
excessive neural activity
Low levels of glycine and GABA can lead to what?
neural overactivity which leads to seizures, unwanted skeletal muscle contractions, and anxiety
What types of transmitters are slow-acting?
amines such as dopamine, norepinephrine, serotonin, or histamine
Is dopamine excitatory or inhibitory?
excitatory or inhibitory depending on receptor type
What are the effects of dopamine?
It is associated with feelings of pleasure, reward, and thus motivates certain behaviors as important as eating, and as destructive as addiction
Is norepinephrine excitatory or inhibitory?
excitatory or inhibitory depending on receptor type
What are the effects of norepinephrine?
It plays a vital role in active surveillance by increasing attention to sensory information
Norepinephrine is essential in producing what?
The “fight-or-flight” response to stress
Excessive levels of norepinephrine can produce what?
panic disorder
Is serotonin excitatory or inhibitory?
usually inhibitory
What does serotonin affect?
mood and perception of pain, adjusts the general arousal level, and an suppress sensory information
The highest levels of serotonin occur with what?
alertness
The lowest levels of serotonin occur with what?
REM sleep
What are the effects of serotonin?
It plays a role in impulsivity, moral decision making, and obsessive-compulsivity
Is histamine excitatory or inhibitory?
usually inhibitory
Where is histamine typically concentrated? Therefore, it is known for doing what?
In the hypothalamus
Regulates hormonal function and increases arousal
How do neuroactive peptides affect neuronal signaling?
By acting as traditional hormones, neurotransmitters, or neuromodulators
What is the most common neuroactive peptide?
substance P
When tissue is injured what does substance P do?
It simulates nerve endings at the site of injury
What does substance P do in the CNS?
It acts as a neurotransmitter carrying information from the spinal cord to the brain
Describe why substance P is strongly implicated as a neuromodulator in the pathophysiologic response to pain?
It involves the perception of normally innocuous stimuli as painful
What is the diffusible slow-acting transmitter?
Nitric oxide
Does nitric oxide require a receptor to bind for activation?
No, it is diffusible
Receptors on the postsynaptic neuron are named after what?
the transmitter/modulator to which they bind
When does a synaptic receptor act directly?
When the receptor and ion channel make up a single functional unit
How does a synaptic receptor act indirectly?
By using a cascade of intracellular molecules to activate ion channels or cause other changes within the postsynaptic neuron
What are the 3 mechanisms postsynaptic receptors use to transduce signals?
- Directly opening ion channels (fast synaptic transmission)
- Indirectly opening ion channels (slow synaptic transmission)
- Activating a cascade of intracellular events, including activating genes (slow synaptic transmission)
What type of ion channel is an example of a direct activation of ion channels?
Ligand-gated ion channels (ionotropic receptor)
What do ligand-gated ion channels consist of?
proteins that function as receptors for the neurotransmitter and as ionotropic receptors
When do ligand-gated ion channels open?
when specific chemical ligand binds to the receptor surface
What type of ion channel is an example of an indirect activation of ion channels?
G-proteins (metabotropic receptor)
How do G-proteins indirectly open ion channels?
By acting as cytoplasmic shuttles, moving between the receptor and target effector proteins on the internal surface of the cell membrane
Describe the sequence of events when a neurotransmitter binds to a G-protein receptor (6 steps)
1) the receptor protein changes shape
2) the G-protein becomes activated
3) the active subunits of G-proteins break free from the receptor to act as cytoplasmic signaling shuttles
4) the subunit binds to a membrane ion channel
5) the ion channel changes shape and opens
6) the subunits become deactivated and reassociated with the receptor
Do the effects of NTs bound to ligand-gated ion channels or G-proteins develop slowly and act longer?
G-proteins
What affects long-acting systems that regulate mood, pain perception, movement, motivation, and cognition?
G-proteins via their second messengers
By activating a cascade of intracellular events via a second-messenger system, what can G-proteins do?
- activate genes, causing the cell to manufacture different NTs or other specific cellular products
- open membrane ion channels
- modulate Ca2+ concentrations inside the cell which regulates metabolism and other cellular processes
In second-messenger systems what is the first messenger? What is the second? What do each do?
- the NT is first; it delivers the signal to the receptor but remains outside the cell
- the second messenger is produced inside the cell; it conveys the message and activates responses inside the cell
Other than having the ability to activate several different down-stream molecules with the binding of a single NT what does a G-protein do?
Dramatically amplify a signal
What is the only effect of a NT binding to a ionotropic receptor?
local depolarization or hyperpolarization of the membrane
What are the 3 effects of a NT binding to a metabotropic (G-protein mediated) receptor?
- local depolarization or hyperpolarization of the membrane
- increase rate of synthesis of specific cellular products
- affect cell metabolism and other processes
What are the 2 categories of ACh receptors?
nicotinic and muscarinic
Are nicotinic receptors ionotropic or metabotropic?
ionotropic (directly open ion channels)
What do nicotinic receptors do?
they allow a rapid increase in intracellular Na+ and Ca2+, producing a local depolarization
Where are nicotinic receptors found?
- at the neuromuscular junction
- at autonomic ganglia
- in some areas of the CNS
Loss of nicotinic receptor-expressing neurons in the brain is a hallmark of what disease?
Alzheimer’s
What kind of receptor are muscarinic receptors?
G-protein receptors (metabotropic)
Activation of a muscarinic receptor produces what?
a slow, prolonged response that may be excitatory or inhibitory
Where are muscarinic receptors found?
- mainly in autonomic effector cells in the heart
- on other autonomic effectors
- in some regions of the brain
Are glutamate receptors ionotropic or metabotropic?
they can be either
What are ligand-gated ion channels that bind glutamate called?
AMPA, kainite, or NMDA receptors
Activation of AMPA and kainite receptors causes what?
fast depolarization of the postsynaptic neuron
Describe the activation of the NMDA receptor
In order for the ion channel to open, glutamate must be bound to the receptor and the membrane must depolarize simultaneously. Therefore it is both voltage- and ligand-gated.
Activation of a NMDA receptor produces what?
the associated channel to open and close very slowly
What are the 2 types of receptors that GABA binds to?
GABA(a) and GABA(b)
Describe GABA(a) receptors
These receptors are inotropic Cl- channels that open when GABA binds to the receptor, producing hyperpolarization of the postsynaptic membrane
Describe GABA(b) receptors
These slow-acting receptors are linked to ion channels via second-messenger systems
What do the 5 dopamine receptors do?
They use second-messenger systems to suppress the activity of Ca2+ channels
Describe the 2 types of NE receptors
- Activation of alpha NE receptors in the gut causes relaxation of intestinal smooth muscle
- Activation of beta NE receptors in the heart increases the force of heart rate contraction
What are agonists?
drugs that bind to the receptor and mimic the effects of naturally occurring neurotransmitters
What are antagonists?
drugs that prevent the release of neurotransmitters or bind to the receptor and impede the effects of a naturally occurring transmitter
What is Lambert-Eaton syndrome?
A disease in which antibodies destroy voltage-gated Ca++ channels in the presynaptic terminal
What is Myasthenia gravis?
A disease in which antibodies attack and destroy nicotinic receptors on muscle cells and because a normal amount of ACh is released into the cleft there is repetitive use of the muscle
What is Channelopathy?
A disease that involves dysfunction of ion channels, which causes some cases of epilepsy and migraine headaches
In summary what are the 2 classes of NTs?
- Small molecule NTs
- Peptide NTs
In summary what are the 2 families of receptors?
- ionotropic (ligand-gated ion channels)
- metabotropic (receptor activating
second-messenger systems)
