2 - Synaptic Transmission & NeuroMuscular Junction Flashcards
Synaptic Transmission
- Major process by which signals are
transferred within nervous system - Synapse
- Site where info is transmitted from 1 cell to
another
2 main types: - Electrically (electrical synapse)
- Chemically (chemical synapse)
Electrical Synapse
- Low resistance pathway between cells that allows current to flow from 1 cell to another
- Gap junctions
- Large pore diameter
- Allows free movement of ions between cells
- 2 hemichannels (connexons)
- Each connexon is a hexamer of connexin protein subunits
- Fast (no synaptic delay)
- Bidirectional (current can flow in either direction)
- Widespread throughout CNS, cardiac muscle, and some smooth muscle
Chemical Synapse
- No direct communication between 2 cells
- Separated by a 20nm spaced called a synaptic cleft
- Unidirectional
- Presynaptic vs postsynaptic
-
Axons synapse onto the dendrites
or soma of 2nd cell (axodendritic,
axosomatic synapse) - Axoaxonic, dendrodentritic, and
dendrosomatic
Briefly the following sequence occurs at chemical synapses:
i. Action potential is propagated down the motor neuron, depolarizing the
presynaptic terminal. This causes voltage-gated Ca2+ channels to open.
ii. Calcium flows into the terminal and uptake causes neurotransmitters to be
released into the synaptic cleft.
iii. The neurotransmitter diffuses across the synaptic cleft to the postsynaptic
membrane (called a motor end plate in NMJ) and binds to receptors.
synaptic vesicles
- Package, store, deliver neurotransmitters
- Vesicles are synthesized in rough ER, matured in Golgi network
- Travel by fast axonal transport to nerve terminal
- Peptide neurotransmitters already loaded into vesicle
- Non-peptide neurotransmitters are loaded at terminal
Chemical Neurotransmitters
- Information transmitted via neurotransmitters
-
Neurotransmitter requirements
1. Must be synthesized by presynaptic neuron
2. Must be stored in presynaptic nerve terminal - Released in sufficient amounts to exert action
3. Substance must be released in response to presynapticdepolarization and release must be Ca2+-dependent
4. Its target (receptors) must be present on postsynaptic cell and must result in postsynaptic electrical activity - NT don’t travel far (<1µm) compared to hormones.
5. Specific mechanism must exist for eliminating
compound from synaptic cleft
Types of neurotransmitters
Non-peptide neurotransmitter uptake
- Non-peptide neurotransmitter are
synthesized locally at nerve terminal &
then loaded into vesicle - Vacuolar-type H+ pump(H+-ATPase)
- Neurotransmitter transporter
- Exchange neurotransmitter for H+
- ACh
- Serotonin
- Norepinephrine
- GABA/glycine
- Glutamate
Action Potential
Resting Membrane Potential:
Voltage Value: Approximately -70 millivolts (mV).
The neuron is at rest, and there is a potential difference across its membrane, with the inside being negatively charged compared to the outside.
Depolarization:
Voltage Value: Around -55 mV.
A stimulus causes the membrane potential to become less negative, reaching a threshold. Voltage-gated sodium channels open.
Rising Phase of the Action Potential:
Voltage Value: Reaches +40 mV.
Sodium ions rush into the neuron, causing a rapid depolarization. The inside of the neuron becomes positively charged.
Repolarization:
Voltage Value: Drops back toward -70 mV.
Voltage-gated potassium channels open, allowing potassium ions to leave the neuron. This restores the negative charge inside.
Hyperpolarization:
Voltage Value: Briefly goes below -70 mV.
Potassium channels may briefly overshoot, causing the membrane potential to become more negative than the resting state.
Resting State:
Voltage Value: Returns to -70 mV.
Sodium-potassium pumps actively restore ion concentrations, bringing the neuron back to its resting membrane potential.
Ca2+ regulated neurotransmitter release
- Action potential induces membrane depolarization
- opens voltage gated Ca2+ channels
- Ca2+ accumulation induces vesicle fusion (synaptotagmin)
- Releases neurotransmitter into synaptic cleft
Transmitter Release
- Vesicle membrane contains several integral
membrane proteins - Synaptobrevin (v-SNARE)
- Forms complex
- Drives vesicle fusion
- Digested by tetanus or botulinum
- Synaptotagmin
- Mediates binding of Ca2+
- Triggers exocytosis
-
Presynaptic membrane contains several
membrane proteins: - SNAP-25
- Syntaxin
A rise in Ca2+ triggers fusion of synaptic vesicles with the presynaptic membrane.
* The SNARE protein, synaptobrevin forms a complex with SNAP-25 and Syntaxin-1
and the 3 SNARE proteins draw the vesicle close to membrane.
* The entry of Ca2+ binds to synaptotagmin and initiates fusion.
A
Ionotropic / Metabotropic Receptors
- Information transduced to postsynaptic membrane by 2 mechanisms
- Ligand-gated ion channels
- G-protein-coupled receptors
Ligand-gated ion channels
- Ionotropic = rapid opening of ion channels (msec)
- This in turn depolarizes or hyperpolarizes the postsynaptic membrane.
-* Nicotinic AchR
G-protein-coupled receptors
- Metabotropic = interact with ion channel proteins or 2nd messenger effector proteins
- Slow, biochemically mediated (sec-mins)
- Metabotropic activation results in the production of active α and βγ subunits which initiate a wide variety of responses. Because of this more complicated system, they are much slower than ionotropic receptors.
- Muscarinic AchR
Neurotransmitter Receptors
Ionotropic Receptors
Ionotropic receptors can depolarize (activate) or hyperpolarize (inhibit) the membrane depending on whether the channel is permeable to cations or anion
Postsynaptic Potentials
- Excitatory PostSynaptic Potential (EPSP)
-Depolarization in postsynaptic cell - At NMJ - End Plate Potential (EPP)
- Inhibitory PostSynaptic Potential (IPSP)
-Hyperpolarization in postsynaptic cell
Bound receptors activate the postsynaptic cell.
* EPSPs result if a post-synaptic membrane is stimulated towards a depolarized voltage
* IPSPs result if a post-synaptic membrane is stimulated towards a hyperpolarized voltage.
* EPSPs aren’t strong enough to reach threshold, therefore many (~50) EPSPs must summate to hit threshold and induce an action potential. Neurons have low safety factors (ratio of EPSP amplitude to threshold amplitude = <1)
EPSP, IPSP & the Action Potential
- EPSPs resulting from the opening of cation channels drive Vm toward depolarized voltages
(EEPSP) and the action potential threshold - IPSPs resulting from the opening of anion channels drive Vm toward hyperpolarized
voltages (EIPSP) and away from the action potential threshold
Safety Factor
- Size of the PSP generated in postsynaptic cell varies
- Strength of synapse quantified by its safety factor
- Ratio of EPSP amplitude to amplitude needed to hit threshold
- Neuronal synapse have low safety factors (ratio<1)
- Takes many summed EPSP to hit threshold
- AP are typically generated at initial segment due to high density of Na+ channels
Synaptic Integration
- A = EPSPs generated by synapses close to initial segment will result in larger depolarizations
- B = temporal summation
- EPSPs separated by a latency less than their duration can sum
- C = spatial summation
- EPSPs generated by different synapses can interact; additive
- D = shunting effect/sublinear summation
- Channels are open at both locations and become leaky; less current left to travel down dendrite
Neurotransmission Termination
- Neurotransmitter must be cleared from the synaptic cleft
- Reuptake
-Co-transporters rapidly remove NT - 2° active transporters
-Found in neurons & glia cells - Enzymatic degradation
-Enzymes rapidly hydrolyze NT - ACh hydrolyzed into choline & acetate
-Acetylcholinesterase (AChE) - Choline recycled to make more ACh
- Failure to terminate leads to postsynaptic
hyperstimulation
-prevents postsynaptic cells from responding
to subsequent synaptic activity
Neuromuscular Junction (overview image) - try to describe the general process
- Chemical synapse between peripheral motor nerve terminals and skeletal muscle fiber
- Structurally and functionally very similar to CNS neurons
- Each axon innervates a separate fiber of skeletal muscle. A motor unit is the axon and the muscle fibers that it innervates.
- The postsynaptic membrane of skeletal muscle has large junction folds that increase surface area and include a high density of AChR and voltage-gated Na+ channels.
- End plate potential is the equivalent of EPSP in neuron. However, 1 action potential in the presynaptic membrane is of sufficient size to cause a large enough depolarization in presynaptic membrane to stimulate muscle fiber (high safety factor: ratio of amplitude
of EPP is higher than amplitude needed to hit threshold). - The high safety factor is due to the fact that there are many more AChR (increased surface area because of junctional folds). Only ~ 200 vesicles of ACH is needed, but more are released and can bind to the multitude of receptors on postsynaptic membrane.
- 1 vesicle of ACh = 1 quanta of ACh = 1 mini EPP. Many mEPP (>200) = 1 EPP = 1 depolarization/action potential.
Synaptic Transmission at NMJ
- Motor nerves have similar structure & function as CNS neurons
- Large junctional folds increase postsynaptic surface area
- Junctional folds adjacent tosynaptic cleft have high density of AChR
- Bottom of junctional folds have high density of voltage gated Na+ channels
Neuromuscular Excitation
- Individual muscle fibers innervated by single motor neurons
- End plate potential
- Equivalent of EPSP in neuron
- Local potential at end plate
- Large depolarization
- 3x as much potential as necessary to stimulate muscle fiber
- Has high “safety factor” (>1)
- Amplitude of EPP is higher than amplitude needed to hit threshold
neuromusclar junction toxin effects
CNS vs. NMJ synapse differences
Properties of Electrical & Chemical Synapses
Comparison of Electrical & Chemical Neurotransmission
Answer: D. AChE inhibitor prevents AChE from removing bound Ach. Therefore, more ACh is
available at the muscle end plates to interact with AchR (receptors).
