SYNAPSES
There are two types of synapses.
A. electrical synapses. The
presynaptic and post synaptic cells are
joined together. The cytoplasms are
connected together. Electrical current
flows directly from pre synaptic cells
to post synaptic cell.
B. chemical synapses. The cells are not physically joined together. Transmission is achieved by the
release of neurotransmitter from pre-packaged vesicles which diffuses, after stimulation, across the
cleft and activate the postsynaptic receptors. No electrical current goes across the postsynaptic cell, it
goes out into the extracellular milieu.
The fact that the cells are
Chemical Conduction: Electrical Conduction: actually joined together means that there’s
- Slow - Fast no way to change the current crossing the
- Adaptable - Stereotyped gap junctions. So if I inject a current in a
- Common - Rare neuron (causing a membrane potential),
- Mediated by receptors - Mediated by gap there will always be almost identical to
junctions the other neuron, even if it’s a somewhat
reduced.
Voltage Gated Calcium Channels
They are like voltage gated sodium channels in the action potential. The difference is they let in
calcium instead of sodium.
Extracellular calcium compared to intracellular is very high. Thus, there is a huge driving force.
When the action potential comes along, the depolarization opens up these channels. Then, this massive
electrochemical gradient means there is a big influx of calcium into the presynaptic terminal.
, That is detected by special proteins which then respond to the rise in intracellular calcium by fusing
with the membrane. And that releases the neurotransmitter into the synaptic cleft. The neurotransmitter
diffuses across where it binds to postsynaptic neurotransmitter receptors.
Classes of Neurotransmitter Receptors
Ligand-Gated Ion Channels
- Integral receptors/ effector proteins
- Fast
- Short response
- Integration (has one excitatory one inhibitory receptor-
their integration together)
- Neurotransmitter directly gates a membrane-spanning
pore.
- 3-5 subunits around a central poer. Each subunit encoded
by separate gene. Different subunits confer different
properties (pharmacological diversity).
- Has several families (Cys-loop receptors and Glutamate)
- Best characterised is the nAChR. Structure resolved to
5A.
- There are no LGIC for dopamine or peptides. nAChRs
- For any neurotransmitter, there are usually both Are composed of 5 subunits.
LGICs and GPCRs. Canonical structure for many LGICs.
- Can be inhibitory (CL-) or excitatory. Muscle AChR made of 2a,b,g,d.
Neuronal nAChRs are mostly a4b2 and a7.
G Protein- Coupled Receptors Each subunit has 4 transmembrane domains.
- Couple to second messengers M2 lines the pore.
- Slow N-terminal domain binds the neurotransmitter.
- Longer duration response M3-M4 loop has sites for phosphorylation.
- Usually modulatory
Tyrosine-Kinase Receptors
- Self-phosphorylating
- Variety of second messengers
- Usually is a dimer of two proteins and have a
phosphorylation site
There are two types of synapses.
A. electrical synapses. The
presynaptic and post synaptic cells are
joined together. The cytoplasms are
connected together. Electrical current
flows directly from pre synaptic cells
to post synaptic cell.
B. chemical synapses. The cells are not physically joined together. Transmission is achieved by the
release of neurotransmitter from pre-packaged vesicles which diffuses, after stimulation, across the
cleft and activate the postsynaptic receptors. No electrical current goes across the postsynaptic cell, it
goes out into the extracellular milieu.
The fact that the cells are
Chemical Conduction: Electrical Conduction: actually joined together means that there’s
- Slow - Fast no way to change the current crossing the
- Adaptable - Stereotyped gap junctions. So if I inject a current in a
- Common - Rare neuron (causing a membrane potential),
- Mediated by receptors - Mediated by gap there will always be almost identical to
junctions the other neuron, even if it’s a somewhat
reduced.
Voltage Gated Calcium Channels
They are like voltage gated sodium channels in the action potential. The difference is they let in
calcium instead of sodium.
Extracellular calcium compared to intracellular is very high. Thus, there is a huge driving force.
When the action potential comes along, the depolarization opens up these channels. Then, this massive
electrochemical gradient means there is a big influx of calcium into the presynaptic terminal.
, That is detected by special proteins which then respond to the rise in intracellular calcium by fusing
with the membrane. And that releases the neurotransmitter into the synaptic cleft. The neurotransmitter
diffuses across where it binds to postsynaptic neurotransmitter receptors.
Classes of Neurotransmitter Receptors
Ligand-Gated Ion Channels
- Integral receptors/ effector proteins
- Fast
- Short response
- Integration (has one excitatory one inhibitory receptor-
their integration together)
- Neurotransmitter directly gates a membrane-spanning
pore.
- 3-5 subunits around a central poer. Each subunit encoded
by separate gene. Different subunits confer different
properties (pharmacological diversity).
- Has several families (Cys-loop receptors and Glutamate)
- Best characterised is the nAChR. Structure resolved to
5A.
- There are no LGIC for dopamine or peptides. nAChRs
- For any neurotransmitter, there are usually both Are composed of 5 subunits.
LGICs and GPCRs. Canonical structure for many LGICs.
- Can be inhibitory (CL-) or excitatory. Muscle AChR made of 2a,b,g,d.
Neuronal nAChRs are mostly a4b2 and a7.
G Protein- Coupled Receptors Each subunit has 4 transmembrane domains.
- Couple to second messengers M2 lines the pore.
- Slow N-terminal domain binds the neurotransmitter.
- Longer duration response M3-M4 loop has sites for phosphorylation.
- Usually modulatory
Tyrosine-Kinase Receptors
- Self-phosphorylating
- Variety of second messengers
- Usually is a dimer of two proteins and have a
phosphorylation site
