Synaptic Transmission

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Synaptic Transmission

• Lecture 6

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SYNAPTIC TRANSMISSION

• What is the nature of the signal that crosses the
  synapse?
• Sherrington
• electrotonic transmission
• Also proved himself wrong
• neural conduction too slow

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SYNAPTIC TRANSMISSION

• Chemical Signal?
• How can it be demonstrated?
• Otto Loewi had a dream
• Frog Heart Preparation
• Vagus nerve
• Stimulate Vagus
• Heart rate slows

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• Stimulate A
• Collect fluid

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B
A
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• Perfuse heart B
• Heart B slows
• chemical vagusstoff

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B
A
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• Repeat w/ accelerator nerve
• Stimulate ---gt HR increases

B
A
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• Stimulation excitation
• Acceleransstoff
• both autonomic n.s.

B
A
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The Prize

• Search for chemical neurotransmitters (NT)
• Criteria
• Synaptic Model

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Synaptic Events

• Action Potential reaches axon terminal
• Chemical substance released
• Neurotransmitter (NT)
• Diffuses across synapse
• Binds to receptor protein
• EPSP or IPSP

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Synaptic Transmission Model

• Precursor transport
• NT synthesis
• Storage
• Release
• Activation
• Termination

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Postsynaptic Membrane
Presynaptic Axon Terminal
Terminal Button
Dendritic Spine
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1. Precursor Transport
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2. Synthesis
enzymes/cofactors
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3. Storage
in vesicles
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Terminal Button
Dendritic Spine
Synapse
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4. Release
Terminal Button
Dendritic Spine
Synapse
Receptors
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Terminal Button
Dendritic Spine
AP
Synapse
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Exocytosis
Ca
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5. Activation
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6. Termination
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6. Termination by... Diffusion
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6. Termination by... Enzymatic degradation
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6. Termination by... Reuptake
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6. Termination by... Autoreceptors
A
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Autoreceptors

• On presynaptic terminal
• Binds NT
• same as postsynaptic receptors
• different receptor subtype
• Decreases NT release synthesis
• Metabotropic receptors
• alters protein synthesis

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Receptor Activation

• Ionotropic channel
• directly controls channel
• fast
• Metabotropic channel
• second messenger systems
• receptor indirectly controls channel

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Ionotropic Channels
neurotransmitter
NT
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Ionotropic Channels
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Ionotropic Channels
NT
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Ionotropic Channels
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Metabotropic Channels

• Receptor separate from channel
• 2d messenger system
• G proteins
• cAMP
• other types
• Effects
• Control channel
• Alter properties of receptors
• regulation of gene expression

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G protein direct control

• NT is 1st messenger
• G protein binds to channel
• opens or closes
• relatively fast

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G protein direct control
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G protein direct control
Pore
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G protein Protein Phosphorylation

• Open or close channels at resting Vm
• NT 1st messenger
• Membrane-associated components
• Receptor
• Transducer
• Primary effector
• Intracellular
• 2d messenger
• Secondary effector

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G protein Protein Phosphorylation
external signal nt
external signal nt
norepinephrine
GS
2d messenger
2d messenger
cAMP
secondary effector
secondary effector
protein kinase
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G protein Protein Phosphorylation
PK
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G protein Protein Phosphorylation
ATP
cAMP
PK
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G protein Protein Phosphorylation
ATP
P
cAMP
PK
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Drug Interaction Terms

• Drugs can act at any step of synaptic
  transmission
• Agonist
• direct
• indirect
• Antagonist
• direct
• indirect

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Drug Interaction Terms

• Competitive vs. Noncompetitive
• Inverse Agonist
• Postsynaptic NT antagonist
• Decrease postsynaptic NT effects
• Presynaptic autoreceptor antagonist
• Increase postsynaptic NT effects