Synaptic Transmission Flashcards
Charles Sherrington
- named the junctions between cells “synapses”
- English physiologist, 50 years of experiments.
- Studied (among other things) motor neurons and the motor cortex.
Synapse:
- functional contact between neurons
There are two types of synapses
- Electrical: direct transfer of ionic current from one cell to another
- Chemical: involves release of chemical neurotransmitters
Gap junctions:
- Electrical currents occur at gap junctions
- Electrical synapse
- Connexins form the connexon, and 2 connexons form a gap junction channel
- 3 nanometers
Electrical synapses at gap junctions:
- Ions pass directly from one cell to another.
- Ions can then change the membrane potential
cells are “electrically coupled”. - Positive charge can pass through gap junctions and depolarize the next cell.
Benefits of electrical synapses
1) Usually bidirectional
- if cell #2 is depolarized, current can pass to depolarize cell #1
2) no “synaptic delay”
- Examples: they can be used for rapid reflexes involving escape rxns.
- AP’s can be fired simultaneously
3) Can synchronize activity of neurons
- brainstem neurons generate rhythmic activity underlying breathing are synchronized by electrical synapses.
– hormone-secreting neurons in the hypothalamus burst of hormone secretion into the bloodstream
Otto Loewi and the discovery of chemical transmission
- Saline stops stimulus. The vagus nerve releases chemicals that contribute to slower heart rate when introduced to stimulus.
Synapses can occur anywhere on the neuron:
- Axo-dendritic
-> on dendrite - Axo-somatic
->cell body - Axo-axonic synapses
-> on the axon of another cell/neuron
One presynaptic terminal can
contact several…
- postsynaptic sites.
- Presynaptic side: “active zone”
-> has a clustering of presynaptic vesicles - Postsynaptic side: “postsynaptic density”
Steps of chemical synaptic transmission
1) Synthesize neurotransmitter
2) Pack the neurotransmitter into vesicles
-> there is also repackaging into vesicles
3) Release the neurotransmitter into the synaptic cleft in response to a
presynaptic action potential
4) Bind the neurotransmitter to a receptor
5) Produce a change in the postsynaptic cell
Major Neurotransmitters: Amino Acids
- Glutamate (Glu)
- Gamma-aminobutryic acid (GABA)
- Glycine (Gly)
Major NT’s: Amines
- Acetylcholine (ACh)
- Dopamine (DA)
- Epinephrine
- Norepinephrine (NE)
- Serotonin (5-HT)
Major NT’s: Peptides
- Substance P
- Neuropeptide Y
- Somatostatin
- Cholecystokinin (CCK)
- Vasopressin
- Oxytocin
Steps of chemical synaptic transmission
1) Synthesize neurotransmitter
2) Pack the neurotransmitter into vesicles
3) Release the neurotransmitter into the synaptic cleft in response to a presynaptic action potential
4) Bind the neurotransmitter to a receptor
5) Produce a change in the postsynaptic cell
Voltage-gated calcium channels
- Ion channels permeable to calcium
- Located in the active zones of the presynaptic membrane.
-> at the axon terminal (NT packaging) - Activated by depolarization of the presynaptic membrane.
- External concentration of Ca2+ is greater than internal Ca2+
Necessary vs. sufficient
- You need calcium in the presynaptic cell to produce an AP in the post-synaptic cell
- Calcium is sufficient to produce (release NT’s) an AP in the post-synaptic cell (depolarization)
Steps of neurotransmitter
release
Synapsin
- reversibly binds to synaptic vesicles
- binds vesicles to actin filaments in the
cytoskeleton - keeps vesicles tethered within the reserve pool
- when synapsin is phosphorylated by protein
kinases, it dissociates from the vesicles - phosphorylation allows vesicles to move to cytoplasmic membrane
SNAREs
- SNAp REceptors
- Family of proteins that controls specific binding
and fusion of membranes. - Responsible for fusing the vesicle to the
presynaptic membrane. - release contents into synapse.
- responsible for fusion
- some SNAREs on the vesicle itself and some are on the membrane.
More SNAREs (1)
- Each SNARE protein has a hydrophobic end that
embeds in the membrane and a longer tail that
projects into the cytosol. - One SNARE protein, synaptobrevin, is in the
membrane of vesicles (also called a v-SNARE) - Two other SNARE proteins (syntaxin and SNAP-
25) are in the plasma membrane (also called
t-SNAREs) - snares bind to each other and pull vesicle closer to the membrane
Toxins that affect SNAREs:
1) Tetanus toxin
2) Botulinum toxin
Both cleave the vSNARE synaptobrevin.
(Some forms of botulinum toxin cleave
syntaxin or SNAP-25).
More SNAREs (2)
-The SNARE proteins allow the vesicle to dock at
the presynaptic membrane.
- Synaptotagmin “senses” calcium increases and
triggers fusion of the vesicle and release of
neurotransmitter.
- Synaptotagmin inserts itself into the membrane
- The vesicle fuses with the membrane and
releases neurotransmitter into the synaptic cleft.
Two types of neurotransmitter receptors:
-Ionotropic receptors = ion channels
- Metabotropic receptors = G-protein coupled receptors
Three classes of ion channels:
- Voltage-gated channels (for example the voltage-gated sodium channel)
- Gap junctions
- Ligand-gated channels (the ionotropic receptors)
- Share a common architectural plan: segments that span the membrane
are arranged around a central axis to form a gated channel for ions
Voltage-gated channels
- Consist of one long peptide with four subunits.
- Each subunit has six membrane-spanning
helicies S1-S6 - S4 helix has charged residues: voltage sensor
- There is a pore loop between S5 and S6 which
dips into the membrane to become
the pore.
Electrical synapses:
- Two connexons form a
gap junction - Pore connects
cytoplasm of two neurons
Ionotropic receptors =
- ion channels
- Transmitter-gated ion channels consist of 4-
5 subunits with a pore in the center. - Ligand-gated channel
Ionotropic receptors or ligand-gated receptors
- Each receptor is composed of four or five subunits
- The neurotransmitter binds to one or more of the subunits
- Each subunit contains four membrane-spanning helices: M1 through M4
The 2nd helix of each subunit (M2)…
Ionotropic receptors
- lines the pore.
Composition of the M2 subunit:
Amino acids
- nAChR alpha1 subunit is permeable to cations
-> Glu - GABAaR alpha1 subunit is permeable to carbanions
-> Arg - GlyR alpha1 subunit is permeable to carbanions
-> Arg
Neurotransmitter-gated channels differ based on:
1) Pharmacology of binding sites: which transmitter binds to the channel and
how do drugs interact with the channel
2) Kinetics of transmitter binding process and channel gating. Duration of the
effect of transmitter binding.
3) Selectivity of the ion channel
4) Conductance of the channel determines the magnitude of the effects
All of these properties are a result of the molecular structure of channels.
Glutamate receptors are ion channels.
- They are permeable to cations (positively charged ions) including Na+ and K+
At -65mV, the driving force on Na+…
- > > driving force on K+.
- The NET current will be a positive current flowing into the cell.
EPSP
- = excitatory postsynaptic potential.
1) a transient postsynaptic depolarization caused by a neurotransmitter.
2) Brings the membrane potential towards the threshold for generating action
potentials. So it’s excitatory.
The point at which there is no current…
- is the reversal potential Erev
- ## The reversal potential for glutamate receptors is 0mV. When the cell’s membrane potential is 0mV, no current will flow through these channels.
Another way to think about reversal potentials:
- The reversal potential of glutamate receptors is 0mV.
- So when glutamate binds to the receptor, it will drive the membrane potential
TOWARDS 0mV.
GABA is a neurotransmitter that binds to
- GABA receptors which are ion channels
permeable only to chloride - Let’s say the cell is “at rest” at -60mV.
The equilibrium potential for Cl- = -65mV
IPSP
- = inhibitory postsynaptic potential
1) a transient postsynaptic
hyperpolarization caused by a
neurotransmitter.
2) Tends to bring the membrane
potential away from the threshold for
generating action potentials. So it’s
inhibitory.
New more precise definitions of excitatory and inhibitory synapses:
- Excitatory synapse: The reversal potential is more POSITIVE than the threshold
for an action potential. The EPSP increases the likelihood that an action potential
will occur. - Inhibitory synapse: The reversal potential is more NEGATIVE than the threshold
for an action potential. The IPSP decreases the likelihood that an action potential
will occur.
The general rule of postsynaptic action is:
- If the reversal potential is more positive than threshold, excitation results; inhibition
occurs if the reversal potential is more negative than threshold.
