L18 Neuromuscular Transmission Flashcards
what happens during a myotatic (myotactic) reflex?
a muscle is stretched
1a afferent fibers are excited in sensory endings
innervate motor neurons in ventral horn of spinal cord
what does each excitatory synapse of 1a afferent release?
glutamate
what do local interneurons release onto motor neurons?
glycine ==> IPSP!
explain reciprocal innervation
excitation of motor neurons for an AGONIST muscle + inhibition of motor neurons for an ANTAGONIST mucle
what receptors are excited in excitation of 1a afferents?
AMPA receptors
where are EPSPs and IPSPs located?
motor neurons + interneurons
where are EPPs located?
end plate potential
created in muscle end plates!
what makes up a motor unit?
- cell body
- axon (myelinated)
- NMJ
- skeletal muscle fibers
how many muscle fibers under the control of one motor neuron does fine motor control need?
small (about 10) - extraocular muscles, hand muscles etc.
how many muscle fibers under the control of one motor neuron that does not need fine motor control?
large (about 2000) - postural muscles
define motor nucleus
cell bodies of motor neurons distributed over a few spinal cord segments
axons leave the cord via ventral roots via spinal nerves then join in the peripheral nerve to reach target muscle
collections of motor neurons = forming a continuous column in the spinal cord
where does the axon lose its myelin?
presynaptic terminal that end with synaptic boutons
they are covered by Schwann cells without myelin = Remak Fiber
define motor end plate
the central region of the muscle fiber that received the synaptic boutons and NTs
how many NMJ (or synpases) do each muscle fiber have?
only one!
what happens at the NMJ?
ACh is released by Ca2+ dependent exocytosis from storage vesicles and binds to its ionotropic receptors in the end plate
every impulse in a motor neuron will release ___ to __ the muscle
ACh
excite!
do any inhibitory synapses exist in muscle fibers?
NO - inhibition of muscle fiber contraction is done by synaptic inhibition of the neuron that innervates it, not by the muscle itself (i.e. glycine to antagonist muscle in myotactic reflex)
what does choline acetyltransferase (ChAT) do?
ACh synthesis
choline + acetyl CoA —ChAT—> ACh + CoA
where does ChAT make Ach
in cytosol of nerve ending
what type of neurons make ChAT?
only cholinergic neurons - histochemical marker for these neurons on NS
why is the life cycle of ACh unusual compared to other NTs?
because it is degraded rapidly in the cleft
what enzyme degrades ACh in the synaptic cleft?
acetylcholine esterase! (AChE)
where is acetylcholinesterase made?
cholinergic neuron
where is acetylcholinesterase tethered to?
the basal lamina!
what transport mechanism is used to absorb choline after AChE breaks ACh down into acetyl + Choline?
co-transport with Na+ ions
where are metabotropic subtypes M1 - M4 located?
abundant in brain and in peripheral tissues
where is metabotropic subtype M5 located?
exclusively in brain but at low levels
what does the fetal form of nicotinic ACh receptor have that is different from adult form?
gamma instead of epsilon
what is the functional different between adult nAChR and fetal nAChR?
adult - permits larger currents but have more frequent opening times with a shorter mean open time
fetal - permit smaller currents but have longer mean open times
the properties of adult nAChR are better suited for what?
fast activation of skeletal muscle fibers!
what are active zones
site of ACh releae which are close to Ca 2+ channels
where are ACh receptors located in the end plate?
junctional folds
what happens when you have a prolonged binding of agonist at nAChR?
further conformational changes in which the channel closes = desensitization ==> normally doesn’t happen because AChE usually breaks ACh down pretty quickly
the EPP spreads ____ with ___ from the end plate
passively
decrement - because of length constant!
what direction does the depolarizing effect of cation flux the open nAChR spread?
in both directions form the end plate
the EPP evoked by a nerve impulse is always sufficient to evoke a _____ at the end plate
muscle impulse
what drugs are responsible for preventing arrival of the impulse at the nerve terminal => flaccid paralysis
tetrodotoxin and saxitoxin
what drugs interfere with exocytosis in the motor nerve terminal?
botulinium, alpha-latrotoxin, w-conotoxin
what is the mechanism of action of nerve gases like sarin and tabun?
irreversibly reduce AChE activity by covalently binding to the enzyme —> ACh effects are prolonged (depolarization) => death by paralyzing respiratory muscles
what drugs have structures that resemble ACh and bind to nAChRs and acts as agonists?
carbacol
nicotine
succinylcholine
*none are degraded by AChE in cleft!
what acts as a reversible competitive antagonist of ACh at nAChRs?
curare
pancuronium
= flaccid paralysis
what irreversibly binds to ACh binding sites?
alpha bungarotoxin
=flaccid paralysis
what is a tx for myesthenia gravis (autoimmune - attack nAChR = small amount)?
neostigmine (atropine is often given with it)
what is a tx for lambert eaton syndrome (autoimmune - attack voltage gated Ca2+ channels)?
4-aminopyridine
neostigmine
what are neuromuscular blocking agents commonly used for?
muscle relaxants during general anesthesia and surgery
what are examples of neuromuscular blocking agents
depolarizing agent = succinylcholine
non-depolarizing agent = pancuronium
where are voltage gated Na+ channels and what do they do?
nodes
AP propagation along axon
where are voltage gated Ca2+ channels and what do they do?
nerve ending
Ca influx = exocytosis of ACh
where are ACh gated channels located and what do they do?
junctional folds at end plate
large depolarization at end plate
where are Na+ channels located and what do they do?
junctional folds
muscle depolarization
where are voltage gated Na/K channels and what do they do
muscle membrane
muscle AP propagation
