Lec 5 & 6 - Synaptic Transmission & NMJ Flashcards
What is the time between arrival of an action potential into the presynaptic terminal and a evoked change in the postsynaptic membrane?
Synaptic delay
What is a connexon?
Specialized proteins that form channels for ion passage that have no synaptic delay and has a bidirectional transmission.
The ___________ terminal converts the electrical signal (action potential) into a chemical signal and releases a neurotransmitter.
Presynaptic
The __________ membrane converts the chemical signal back into an electrical signal.
Postsynaptic
What are some factors of electrical synapses?
Ex: heart cells
- Electrical contact
- Minimum synaptic delay
- Bidirectional
- Allows for synchronous activation
What are some factors of chemical synapses?
Ex: Neuromuscular junction
- Chemical
- 0.5-1.0 msec delay
- Unidirectional
What is a jeuromuscular junction?
Synapse between a motor neuron and a skeletal muscle fiber. Its presynapting ending is filled with vesicles containing Ach. The postsynaptic membrane has junctional folds that contain ACh receptors and acetylcholinesterase (AChE) that hydrolyzes ACh and stops its action.
What is Lambert Eaton syndrome?
Disruption of Ca2+ channel function by autoantibodies causes muscle weakness.
What are the steps in the presynaptic NMJ events?
- Action potential travels down axon to presynaptic membrane
- Membrane depolarizes and opens voltage dependent Ca2+ channels, allowing Ca2+ to rush in
- Ca2+ influx
- Ca2+ influx promotes binding of synaptic vesicles to inside membrane of presynaptic terminal
- ACh is released via exocytosis
- ACh diffuses across synaptic cleft and combines with ACh receptors on post junctional membrane
What are the steps in postsynaptic NMJ events?
- ACh binds with the nicotinic receptor and causes opening of ligand-gated cation channels (Na/K) in the postsynaptic membrane
- Sodium ions rush in to the cell and causes graded depolarization - producing endplate potential (EPP)
- Muscle membrane surrounding the endplate depolarizes and produces an action potential which propagates away from the endplate in both directions
Acetylcholine is broken down by acetylcholinesterase into what products?
Acetate and Choline (which is taken up by presynaptic terminal for resynthesis of Ach)
How is acetylcholine made in the presynaptic cell?
Choline + Acetyl Co-A
What toxin blocks the action of ACh by binding to the ACh receptor?
Curare (plant alkaloid) - This causes a decrease in EPP. This mimics the autoimmune neuromuscular disease Myasthenia gravis
Acetylcholine is a natural agonist for what two cholinergic receptors?
Nicotinic and Muscarinic
What does Neostigmine do?
Inactivates acetylcholinesterase which causes and increase in EPP
What occurs when someone has myasthenia gravis?
Destruction of ACh receptors which causes a decrease in EPP and can lead to lack of AP being formed. This is due to specific antibodies made by the immune system of the patient.
What are some cardinal features of myasthenia gravis?
Fluctuating fatigue of voluntary muscles, which worsen after exertion and improve with rest. Initially it involves weakness of the extraocular muscles. Ptosis (eyelid drooping) is very common, especially during long periods of driving or reading.
Ptosis and failure to close eyelids indicates paralysis of the orbicularis oculi muscle innervated by CN ___.
CN VII (facial)
T/F - Weakness of the extraocular muscles may resemble paralysis of CN III, IV, and VI.
TRUE
What is used to treat myasthenia gravis and curare?
- AChE blockers
- Stigmines (neostigmine, pyridostigmine, etc.) They prevent breakdown of ACh and improve neuromuscular transmission.
T/F - Myasthenia gravis affects pupillary function.
FALSE - MG does NOT affect pupillary function but CN III palsy does.
Why doesn’t MG affect the muscles of the heart and intestine?
f
Someone with severe fatigability, weakness during mastication (can’t keep jaw closed after chewing), nasally speech (weakness of soft palate), and slurred speech without difficulty in language fluency may have……
myasthenia gravis
__________________________ can cause abnormalities in eye position or movement, visual problems due to optic neuritis (inflammation of the myelin sheath of the optic nerve).
Multiple sclerosis
What disease causes nerve degeneration with asymmetric muscle weakness and atrophy?
Amyotrophic lateral sclerosis
What disease causes nerve degeneration?
Polio
What is a type of demyelination diseases that affects a variety of nerves, so sensory symptoms are possible?
Guillain-Barre syndrome
What disease prevents ACh release via autoantibodies at the neuromuscular junction?
Lambert-Eaton myasthenic syndrome
What does botulism do?
Prevents ACh release - it affects all ACh junctions, causing autonomic symptoms including dilated pupils, relaxation of muscles.
What is Botulinum used for?
Treatment of strabismus (eyes don’t line up properly), blinking distonia (twitchy eyes) , myofacial pain, severe bruxism (grinding of teeth), masseter hypertrophy, pain in masticatory muscles, neuromyotonia (aka: isaac’s syndrom - spontaneous muscle spasms), and Sialorrhea associated with stroke or parkinson’s disease (excessive drooling).
What does the black widow spider venom contain and what does it do to the human body?
Alpha-latrotoxin depolarizes cell membranes, inducing massive calcium influx in the presynaptic terminal of the neuromuscular junction and release of acetylcholine causes pain and muscle cramping.
Are both the NMJ and CNS excitatory and inhibitory?
No - only the CNS does both, the NMJ only is excitatory.
T/F - Excitatory postsynaptic potential (EPSP) increases the number of APs and Inhibitory postsynaptic potential (IPSP) decrease the number of APs.
TRUE - EPSPs cause depolarization and IPSPs cause hyperpolarizations
How do IPSPs work?
They work by opening K+ channels (K+ out) or Cl- channels (Cl- in), causing hyperpolarization.
What are some typically inhibitory neurotransmitters?
GABA and glycine
When GABA binds to GABAa ionotropic receptors, it opens ___ channels.
Cl-
When GABA binds to GABAb metabotropic receptors, it opens ___ channels.
K+
Valium the drug facilitates (increases the efficacy) of _______.
GABA
How does valium act on the human body?
Valium is a benzodiazepine drug. This drug increases the efficacy of GABA, leading to an increased number and duration of IPSP which then causes a relaxed feeling.
Action potentials originate where?
Trigger zone - aka: Axon hillock
EPSP and IPSP are graded/all-or-none potentials?
Graded
What is spatial summation?
It occurs when two separate inputs arrive at the same time (a stimulus). It includes the inputs of the same sign added to one another and inputs of the opposite sign subtracted from one another
