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Advantages (and dis) of electrical synapses (CH 13Summary #1)
- Role: Mediates Fast, synchronous action
- Advantages
- 1: current flow is INSTANTANEOUS
- 2: current flows EITHER DIRECTION (not polarized)…could be DISadvantage
- 3: Continuity between cells via GAP JXNS bridged by CONNEXON protein CHANNELS
- Disadvantage
- 1: Electrical synapses ALWAY Excitatory (not inhibitory)
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Chemical Synapses properties
- 1: 20-30nm synaptic cleft connecting (barrier to DIRECT communication)
- 2: Pre-synaptic bouton contains Neurotransmitter molecules stored in SYNAPTIC VESICLES
- 3: Post-synaptic neuron holds RECEPTOR MOLECULES to bind to neurotransmitters
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Zones on a Synapse
- Active zone: site of vesicle release
- Post-synaptic densities: sites of high neurotransmitter RECEPTORs
- Scaffold proteins: aid in organizing proteins and receptors at synapse
- Dendritic spines: Site of Excitatory Synapses-Allow for INCREASED Surface Area for signals
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Steps involved in Chemical Synapse and 2 types of receptors (Ch 13 Summary #8)
- 1. Ca enters: Action potential Depolarizes axon terminal OPENING Ca Channels for Ca Entry to cell
- 2. Vesicle fusion: Ca ions trigger vesicles to fuse to active zones on bouton
- 3. Ionotropic: Ion neurotransmitter receptors OPEN allowing IONS into post-synaptic cells (ie Na entry causes DEpolarization of post-syn)
- 4. Metabotropic: Metabotropic receptors (GPCRs) are activated by neurotransmitters to initiate cascade of eents to produce 2nd messengers (cAMP)
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Advantages of Chem Synapses
- 1: Can be excitatory OR inhibitory
- 2: Can only interact ONE WAY
- 3: AMPLIFICATION Of POST-Synaptic CURRENT Flow: release of vesicles and transmitters can open MANY channels to amplify
- 4: MODIFIABLE in their properties (vs electrical syn)
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2 Neurotransmitter effects
- EPSP: Excitatory post-syn potential allows for Depolarization (ie: Glutamate - opens channels to allow for Na and K to go INTO post-syn cell)
- IPSP: Inhibitory post-syn potential cause HYPERpolarization (ie: GABA diffuses to Post-syn membrane and allows for CHLORIDE ENTRY into Post-syn cell)
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Temporal and Spatial summation
- Can combine both IPSP and EPSPs generated
- temporal: combination of SAME nerve repeatedly stimulating rapidly
- spatial: combination of simultaneous EPSPs occurring at DIFFERENT nerves
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Actions at neuromuscular jxn
- Neurotransmitter is Acetylcholine (located in vesicles)
- Diffuses into post-syn receptors where it BINDS
- Allowing for Na entry into post-syn cell and K moves out (DEPOLARIZATION)
- Action potential is Triggered!
- REUPTAKE of ACh by Acetylcholinesterase breakdown into choline
- Choline moves through choline transporter on pre-syn membrane
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Neuroreceptor release STEPS
- 1. Tethering: Quanta packets move towards Active Zone, attaching REVERSIBLY to SNARE proteins on membrane
- 2. Docking: Quanta vesicles bind to t- and v-SNARE IRREVERSIBLY
- 3. Priming: Ca enters via channels (Depolarization causes this) and binds to Synaptotagmin..triggering
- 4. Fusion: Ca-synaptotagmin causes CONFORMATIONAL change leading to fusion with the membrane and exocytosis of neurots
- 5. Endocytosis of vesicle: ATP dependent with association of protein Clathrin
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Quanta
Vesicles releasing neurotransmitters, each contain several 1000 neurotransmitters
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Neurotransmitter Example types
- Small molecule neuotransmitters:
- Acetylcholine and Glutamate (most fast EPSPs): ionotropic (causes EPSPs)
- Dopamine: metabotropic (G protein - causes IPSPs)
- GABA (most fast IPSPs): Ionotropic (causes IPSPs)
- Also peptide neurotransmitters: multiple known
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Neuron and neurotransmitter release
Neurons can release multiple neurotransmitters, usually 1 small molecule and multiple peptide transmitters
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Peptide vs Small molecule neurotransmitters
- Peptide are produced in Neuronal cell body vs at axon terminal w others
- Peptide inactivated by peptidases vs reuptake or enzymes w other
- Peptide has HIGH freq stim vs slow w other
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Criteria for identifying if there is a NEUROTRANSMITTER at a particular site (Ch 13 SUMMARY #5)
- 1. NT must be be PRESENT at pre-syn terminal and
- 2. RELEASED upon pre-syn stimulation
- 3. NT when added to extracell space must mimic effects of pre-syn stimulation
- 4. MECHANISM for REMOVAL of NT should exist
- 5. DRUG EFFECTS on NT may aid in determinig
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Why are there multiple receptor subtypes for each neurotransmitter? (Ch 13 SUMMARY #7)
- Receptors are used to mediate MULTIPLE Effects, in some cases by the same receptors (ie; ACh receptors - example below)
- ie: In Skeletal muscle, ACh receptor stimulated by nicotine (nicotinic receptor) works to aid in excitation via EPSPs
- In heart muscle, ACh receptor stimulated by Muscarine (muscarinic receptor) aids in IPSPs
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Why are there so many neurotransmitters (evolutionarily) (Ch 13 SUMMARY #6)
- There are evolutionary similarities among vertebrate also found in Nervous system of invertebrates (ie GABA, dopamine, seratonine)
- These neurotransmitters have been evolutionarily conserved, but their ROLE may be different depending on the organism
- Even peptide neutrotransmitters have been shown to have similar protein families showing their importance evolutionarily
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Ligand-gated Channel characteristics (ionotropic)
- RECEPTOR is the CHANNEL
- 1. Opening is ALL or NOTHING
- 2. Probability of opening is DEPENDENT on NT
- 3. Ionic current thru channel provides Synaptic POTENTIAL
- 4. Currents can be SUMMATED to equal synaptic current
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Example of Ionotropic receptor
- Nicotinic ACh receptor
- Contains five alpha subunits surrounding ion channel
- Requires binding of 2 NTs allowing opening to contribute to PSP
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Metabotropic vs ionotropic action difference
- METABO: Indirect mode of action (GPCR). Produces Slow, but LONG Lasting effect
- IONO: DIRECT mode of action (ion channels). Produces Fast, Short effects
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Example of Metabotropic receptor
- Norepinephrine acts on GPCR
- GPCR activates G-protein
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G-protein structure and role
- has alpha, beta and gamma units
- a-subunit releases GDP when activated, in exchange for GTP
- a-subunit dissociates from rest and binds to adenlyl cyclase
- cyclase converts ATP to cAMP
- cAMP ACTIVATES cAMP protein kinases
- These kinases PHOSPHORYLATE proteins, such as MEMBRANE, CYTO or NUCLEAR proteins
- ION Channels: G-proteins can activate them DIRECTLY
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ACh inhibitory action example
Muscarinic ACh receptors act as GPCRs to act with INHIBITORY action
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Habituation and Sensitization
- Habit: DECREASE in reflex response when stimulus is repeated
- Senz: ENHANCEMENT of reflex response to stimulus, when 2ND novel stimulus presented
- ie Aplysia fish, gills amplitude of withdrawl diminishes with repeated repeated low freq stim but when hit on the head the response to stim of gills is large again
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How habituation and sensitization works (neuronal level)
- Habit: DECREASE in QUANTA number (so less neurotransmitters released) due to Inactivation of Ca Channels
- Senz: the sensitizing stimulus INCREASES Amount of NT released Per Impulse, due to INCREASED Ca Influx
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NMDA Receptors as IONOTROPIC or METABOTROPIC (Ch 13 SUMMARY #9)
- BOTH
- First, Ionotropic: Produces EPSPs, but ONLY work when post-syn is DEPOLARIZED (AMPA receptors aid in depolarization allowing Na entry)
- ActioN: Glutamate activates NMDA receptor, but Mg blocks the ion channel. DEPOLarization causes release of Mg into synapse, and then Ca and Na can flow in (and K out)
- Then, METABOTROPIC: The Ca that it allow into the post-syn cell acts as 2nd Messengers to activate Ca dependent protein kinases and allow more AMPA vesicles (containing AMPA glutamate receptors) to fuse to membrane to generate ENHANCED POST-SYN response
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Long term potentiation in hippocampus
Long-lasting ENHANCEMENT of Synaptic transmission following INTENSE long-lasting stimulation
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