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Excitable cells often turn electrical
activity into what?
Ca2+-driven process mediated by voltage-sensitive Ca2+ channels.
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What are connexons?
- Connexons are pair of hemichannels that makes up a gap junction.
- made up of 6 identical connexin subunits
- connexin: 7.5 nm long, has 4 membrane spanning regions
-
Current injected into the large presynaptic fiber produces an AP where?
in postysynaptic cell.
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Most electrical synapses allow current flow in ______ across the synapse.
both directions
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What are the 4 advantages of electrical synapses?
- 1. speed
- 2. coordinating activity in large groups of cells.
- 3. allow transfer of metabolites between cells.
- 4. gaps junctions can close in response to unfavorable conditions.
-
Where are gap junctions found?
in most multicellular tissues.
-
What is Charcot-Marie-Tooth?
A disease where connexin32 is defective. Demyelinating.
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Connexin26 mutations in the epithelial cells of the inner ear lead to what?
deafness.
-
What is oculodentodigital dysplasia?
Defective connexin43. Enamel hypoplasia, craniofacial anomalies and cardiac dysfunction.
-
Describe the significance of 1921 Otto Loewi experiment with the frog heart.
It proved that there is chemical transmission
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What is the significance of the experiment in 1936 by Sir Henry Dale?
He found acetylcholine (ACh) was released by the motor nerve innervating skeletal muscle.
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Describe the steps in chemical synaptic transmission.
- 1. Arrival of an action potential (AP) at presynaptic
- terminal leads to depolarization and opening of voltage-gated Ca2+ channels.
2. Ca2+ enters the presynaptic terminal. The Ca2+ concentration near active zone increases.
- 3. Ca2+ causes vesicles to fuse with the presynaptic
- membrane. Neurotransmitter (NT) is released into the synaptic cleft (exocytosis).
- 4. NT
- molecules diffuse across the synaptic cleft and bind to postsynaptic receptors.
- 5. Receptor
- binding leads to the opening of ion channels, a change in current flow through
- the post-synaptic cell and the generation of the post-synaptic potential.
-
What are receptors?
- Proteins that span the membrane. They have an extracellular site that recognizes and binds NT.
- Have an effector function: typically gate the opening or closing of ion channels (can excite or inhibit)
-
What is the difference between ionotropic and metabotropic receptors?
- ionotropic receptros: have direct effects on ion channels
- metabotropic receptors: have indirect, slower actions thru 2nd messenger systems
-
Describe the end plate.
- axon of the motor neuron loses its myelin sheath and divides into several branches
- ACh is released from small clear vesicles in the boutons into the junctional folds of the underlying postsynaptic muscle fiber.
-
What are the 3 types of neuro muscular junction proteins?
- 1. nicotinic ACh receptors: at the top of junctional folds at a density of about 10,000 receptors per micrometer2
- 3. Acetylcholinesterase: enzyme that causes the hydrolysis of ACh. Present in the synaptic cleft.
-
ACh diffuses and binds to the postsynaptic _____
receptor-channel complex after the ACh release.
nicotinic
-
What generates the end plate potential?
- The opening of ion channels allows the flow of Na+ and K ions across the postsynaptic membrane.
- The depolarization is usually large enough to open sodium channels and trigger an AP in the muscle.
-
What does curare do?
- Block the binding of ACh to receptors.
- the potential is largest at the end plate region and decays with distance along the muscle fiber.
-
What is the significance of the patch clamp technique was used on the 1976 Neher and Sakmann?
They recorded the opening and closing of single ACh - gated channels in muscle cells.
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Nicotinic ACh receptor-channel requires ____ molecules of ACh to bind and change the conformation for sodium to come in.
two.
-
What is alpha - bungarotoxin?
- Toxin from snake venom.
- binds irreversibly to alpha subunit and blocks the ACh receptor.
-
What is Botulinum Toxin?
- Neurotoxin produced by Clostridium botulinum bacteria.
- can be ingested or inhaled
- exists as toxin or spores
- causes muscle paralysis
- blocks release of ACh at the neuromuscular junction by clipping SNARE proteins
-
What is Myasthenia gravis and what happens biologically?
- it is an autoimmune disease
- antibodies are made to the neuromuscular ACh receptor
- Ab blocks the receptors which decreases the number of functional receptors
- results in muscle weakness
-
What are the symptoms of Myasthenia gravis?
- drooping eyelids (ptosis)
- double vision (diplopia)
- difficulty speaking (dysarthria)
- difficulty swallowing (dysphagia)
-
What is the treatment for Myasthenia gravia?
cholinesterase inhibitors inactivate acetylcholinesterase in the synaptic cleft and extend the life of ACh
-
Which is faster, electrical or chemical transmission?
Electrical is much faster.
-
Explain the difference in synapse structure of electrical vs. chemical transmission.
- Electrical synapse: cytoplasm is continuous with distance between pre/post is 3nm.
- chemical transmission: no cytoplasmic continuity, cleft is 20-40 nm wide.
-
Which transmission is bidirection and which is unidirectional? Which allows amplification?
- Bi-directional - electrical
- unidirectional: chemical
- amplification: chemical
-
What are the 4 criteria to be a neurotransmitter?
1. Synthesized in the neuron.
- 2. Present in presynaptic terminal, released in sufficient quantities
- to effect a change in postsynaptic/target structure.
- 3. Mimics action of endogenous substance when applied
- externally.
- 4. Specific mechanism exists for removal from its site of
- action.
-
What are the 2 broad classes of neurotransmitters?
- 1. small molecule: rapidly acting transmitters. ex. ACh, glutamate
- 2. Neuroactive peptides: slowly acting transmitters. Ex. gastrin, angiotensin II
-
Describe the types of synaptic vesicles.
- 1. small: for glutamate, ACh, GABA
- 2. large: dense core vesicles
-
What is the co-release of the neurotransmitters? What about the adrenal medulla?
- the release of small molecule trasnmitter and neuropeptide are both released from a large, dense-core vesicle.
- Adrenal medulla contains secretory
- granules, similar to dense-core vesicles, epinephrine is released directly into
- the bloodstream.
-
each neuron must sum or _______ the information it receives and produce an output signal.
integrate
-
Synapses which are excitatory are often found on ______. Inhibitory synapses are often found on the _____.
-
What is axon hillock?
- The initial segment of the axon and the site of AP generation.
- Na+ channels are concentrated in the initial segment
- passive membrane properties will also affect the summation of synaptic inputs
-
Effectiveness of chemical synapses can be altered in the short term or long term by what 2 ways?
- a. changes within the neuron
- b. extrinsic factors : input from other cells
-
What is the most common excitatory transmitter in the central nervous system (CNS)?
L-glutamate
-
What are the 3 types of ionotropic glutamate reeptors that mediate excitatory responses?
- AMPA : blocked by CNQX
- Kainate : blocked by CNQX
- NMDA : blocked by APV
-
What does the metabotropic glutamate receptors do?
- Mediate excitatory or inhibitory response.
- the binding to this receptor stimulates PLC leading to formation of 2nd messengers DAG and IP3.
- activated by amino cyclopentadicarboxylic acid (ACPD)
-
Which receptors involve in the early part of the excitatory post-synaptic potential (EPSP) and which involves in the late phase?
- Early part of EPSP: AMPA/kainate
- Late part of EPSP: NMDA
-
What are the 3 unusual features of the NMDA receptor?
- 1. High conductance channel opened by NMDA is permeable to Ca2+ as well as Na+ and K+.
- 2. Glycine required as cofactor for channel opening.
- 3. at hyperpolarized potentials Mg2+ blocks the channel. At the cell's resting potential, Mg2+ enters the receptor-channel and binds tightly. Following a depolarization, Mg2+ is ejected from channel allowing Na+ and Ca2+ to enter cell.
-
NMDA is _____ current. AMPA is _____ current.
-
what happens when presynaptic neuron fires repeatedly?
- EPSP will summate => larger depolarization => more Ca2+ will eneter the cell => triggers Ca2+ dependent processes
- this process is thought to be involved in learning and memory
-
What is spatial summation?
when 2 or more presynaptic inputs arrive at the same time at the postsynaptic cell and act at different sites
-
What is temporal summation?
when 2 or more consecutive presynaptic inputs at the same site are added together in the postsynaptic cell.
-
What is excitotoxicity?
- Too much glutamate = toxic
- excess Ca2+ to enter through the NMDA receptor
- lead to stroke, seizures, neurodegeneration and cell death
-
Which type of receptor mediate inhibitory transmission?
-
Describe the function of GABAA receptor.
- ionotropic receptor that gates the Cl channel
- ECl = -90 mV
- cell's resting potential is more positive than that
- net influx of Cl
- leads to hyperpolarization (inhibition)
-
What is GABAB?
- metabotropic receptor
- activates K+ channels
- outwards K current results in hyperpolarization
- Ca2+ channels may be inhibited via 2nd messenger pathway
-
What does glycine do?
- activates ionotropic receptors that open Cl channels
- strychnine and tetanus toxin block glycine receptors
- when glycine is blocked, muscle spasms occur => opisthotonos
-
What is the structure of GABAA receptor?
- composed of 5 subunits
- 2 alpha, 2 beta, 1 gamma
- subunits are similar and GABA can bind any one
-
What is the glycine receptor?
- 3 alpha and 2 beta subunits
- glycine binds to the alpha subunits
-
What is benzodiazepines?
- is a drug that bind to the gamma subunit of the GABAA channel
- increase Cl conductance thru the channel
-
alcohol and barbiturates ______ the effect of GABA.
enhances
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