Synapse and Neurotransmitters Flashcards
What is a synapse?
Contact between a neuron and another neuron or its effector cell
- Pre-synaptic neuron (axon) - Post-synaptic neuron (dendrite or cell body) OR a cell (ie. muscle) - Cells separated by the synaptic cleft
CHEMICAL Synapses (7)
- Predominant type of synapse
- Unidirectional
- Uses neurotransmitters
- Fast (ionotropic) or slow (metabotropic)
- Signal can be amplified
- Can be excitory or inhibitory
- Short term effects
- Metabolism of neuron can be changed altering the properties of the synapse
Neuroactive Peptides (4)
- Made in cell body, transported to axon terminal
- Found in brain and ENS
- Chains of AAs
- Metabotropic receptors
Small-molecule Neurotransmitters (4)
- Made in axon terminals
- Amino Acids
- glutamate, glycine
- Amines
- Acetylcholine
- norepinephrine
- Metabotropic OR Ionotropic receptors
Key Criteria to be a Neurotransmitter (4)
- Must be present in the pre-synaptic terminal
- Released upon stimulation (depolarization and calcium)
- Neurotransmitter in extracellular fluid must elicit same response as the synaptic event
- Mechanism for removal must exist
Neurotransmitters may elicit a variety of post-synaptic responses
Dependent on receptor types (ionotropic vs. metabotropic), which is dependent on cell type
Neurotransmitters are active for a ____ time.
SHORT
Small-molecule NT:Enzymatic destruction
Re-uptake
-Independent from vesicular re-uptake
Neuroactive Peptides: Extracellular peptidase digestion
IONOTROPIC Chemical Synapses (4)
Directly alter membrane permeability to ions (open/close ion channels)
Signal transduction
Fast
Excitory and Inhibitory effects
METABOTROPIC Chemical Synapses (4)
Produce a metabolic change in the post-synaptic cell (usually with secondary messengers)
Modulation of neuronal function
Slow
Excitory, Inhibitory and other (cytoplasmic) effects
Basic overview to chemical synapses
- Neurotransmitter released into synaptic cleft
- Binds receptor on post-synaptic effector (neuron or target cell) and alters post-synaptic cell function
How is the neurotransmitter released? (3)
- Neurotransmitter is synthesized in pre-synaptic cell
- Stored in vesicles at either the active site or interior of axon terminal
- Each vesicle contains ~5,000 neurotransmitter molecules
- Quantal packets
- Release requires membrane depolarization and calcium influx
How is the neurotransmitter released? (Last 2)
-Depolarization of the axon terminal opens voltage gated calcium channels
-Action potential travelling down axon reaches the axon terminals and depolarizes the membrane
-Influx of Ca2+ when the channels open
-Un-depolarized neurons have very low
Ca2+ concentrations in the cytosol
-Ca2+ influx into the cytosol triggers exocytosis of vesicles
-Vesicles fuse to the plasma membrane
-Neurotransmitter released into synaptic cleft
Ligand-gated Channels (4)
-Synaptic transmission (fast, ionotropic)
-Permeability dependent on neurotransmitter
binding (voltage independent)
-Located on dendrites and cell body
-Generate potentials that are graded and spread
decrementally (length constant)
Voltage-gated Channels (4)
- Action potential generation (Na+ and K+ channels on axon)
- Neurotransmitter release (Ca2+ channels in axon terminal)
- Permeability dependent on membrane potential (voltage dependent)
- Generate potentials that are “all or nothing” and propagated
Synaptic Potentials (4)
- Occur in ionotropic synapses (ones that involve a change in membrane permeability in the post-synaptic cell)
- Graded change in post-synaptic neuron’s (or cell’s) resting membrane potential
- PSP = post-synaptic potential
- Not an action potential- only small changes in membrane potential… one alone is not enough to reach threshold
- Inhibitory (IPSP) or excitory (EPSP)
- Inhibitory: hyperpolarizes (makes more “–” than resting)
- Excitory: depolarizes (makes less “-” than resting)
A single nerve stimulated in rapid succession- continues to release NT
Temporal Summation
Several pre-synaptic neurons acting on the same post-synaptic neuron are stimulated simultaneously
Spacial Summation
Summation of PSP (Post-synaptic potential)
Each individual synapse (the effect 1 action potential’s NT binding) depolarizes (or hyperpolarizes) the membrane only very slightly
-Not enough to generate an action potential in the post-synaptic cell
Axodendritic
Synapse with dendrite = farther from hillock = less influence
Axosomatic
Synapse with the cell body = closer to hillock = more influence
Proximity of synapse to axon hillock (hillcock)
- Spread of PSP from the dendrites or cell body to the site of the action potential is passive
- The further from the axon hillock, the more the PSP is degraded
Neuronal Integration:
Whether or not an action potential is generated in the axon is dependent on…
-Spatial and temporal summation
Overall effects of all of the pre-synaptic neurons acting on a post-synaptic neuron (or cell)
Some may depolarize, others may hyperpolarize
-Proximity of synapse to axon hillock (hillcock)
Post-synaptic membrane permeability (3 Scenarios)
- Neuromuscular junction (EPSP)
- Excitory (Type 1) synapse (EPSP) in the CNS
- Inhibitory (Type 2) synapse (IPSP) in the CNS
Key features of a fast ionotropic receptor (4)
- Channel opening is all or nothing
- Channel opening depends on neurotransmitter concentration
- More NT = more opening - Current flowing through channels contributes to neuron’s PSP
- Currents through all channels can be summated
- Can add to each other (if both IPSP or EPSP) or cancel each other out
Sum of all ion currents flowing through channels at once
-Source of the EPSP/IPSP
Synaptic current
Acetylcholine = neurotransmitter
- Binds to a ligand-gated Na+/K+ membrane channel
- Increases membrane permeability to BOTH Na+ and K+
- Na+ flows in more rapidly than K+ flows out—WHY??
Membrane depolarizes
Neuromuscular EPSP
Synapse between a neuron and a skeletal muscle fiber (somatic nervous system)
Relay synapse (3)
- Each motor neuron action potential causes a large EPSP in the muscle
- Lots of neurotransmitter released from pre-synaptic neuron
- Generates a muscle action potential (muscle depolarized and contracts)
Type 1 synapse (ionotropic) = Fast EPSP
- Similar mechanism to neuromuscular EPSP
- Smaller in magnitude, but results in membrane depolarization due to opening of the ligand gated Na+/K+ channels
- Neurotransmitters:
- ie: Glutamate (in CNS)
- Smaller EPSP than neuromuscular
- Only 1-2 vesicles released per synaptic transmission = less NT released = lesser effect on post-synaptic cell membrane potential
- 1 EPSP does not depolarize the post-synaptic membrane enough to generate an action potential
- NEED SUMMATION
Type 2 synapse (ionotropic)= Slow IPSP
- Inhibitory- hyperpolarizes membrane
- Makes it harder for the neuron to reach the threshold membrane potential and generate an action potential
- Neurotransmitters:
- ie. GABA and glycine (in CNS)
- Involves opening of ligand-gated chloride channels
- Cl- floods in, making the inside of the cell more negative than resting membrane potential = HYPERPOLARIZES
- Makes it harder to reach threshold and generate an action potential
- Cl- floods in, making the inside of the cell more negative than resting membrane potential = HYPERPOLARIZES
Key mechanisms of slow metabotropic receptors
- G Protein-coupled receptors (GPCR)
- Receptors are NOT ion channels as in ionotropic receptors
- GPCR can move through the fluid membrane and interact with other proteins- trigger effects within the neuron
- When neurotransmitter is bound, can initiate signaling cascades (usually with cAMP)
- Phosphorylate membrane proteins (including ion channels- indirect effect on membrane permeability)
- Phosphorylate cytoplasmic proteins- alter neuron function
- Phosphorylate nuclear proteins- alter neuron function
- When neurotransmitter is bound, can initiate signaling cascades (usually with cAMP)
Other Metabotropic Regulatior Mechanisms
- Secondary messenger does not have to be cAMP to cause phosphorylation
- cGMP
- via Phospholipase C: DAG, IP3 and Ca2+
- Some GPCR can act without a secondary messenger
- Interact directly with ion channels
- Can be depolarizing (EPSP) or hyperpolarizing (IPSP), but these effects are slower than ionotropic channels
- Also possible to have no effects on membrane permeability but to alter neuronal function or properties without contributing to the PSP
Neurotransmitter release relies on TWO THINGS
- ) Axon terminal depolarizes –> Action Potential (AP) reaches terminal
- ) Ca2+ enters axon terminal (ESSENTIAL)
Post-synaptic (MORE/LESS) likely to generate action potential
LESS
Integration
Post synaptic neuron takes all incoming PSP information and “decides” whether or not it will have an action potential
