Neuromuscular Junction: Receptors, Muscle Contraction, and Drugs

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Added on  2023/01/06

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This report provides a comprehensive analysis of the neuromuscular junction, focusing on the processes of neurotransmission and muscle contraction. It explores the receptors expressed on the postsynaptic cell, particularly glutamate receptors like NMDA, AMPA, and kainite, and details the role of acetylcholine in neurotransmission. The report also discusses the requirements for muscle contraction, including neural stimuli, calcium ions, and ATP. It then examines the effects of drugs such as neostigmine and adrenaline, comparing their impact on muscle reactivity and analyzing dose-response curves, specifically for suxamenthonium. The report further compares the effects of tubocurarine and neostigmine, highlighting their mechanisms of action and impact on muscle function, and concludes by summarizing the key findings regarding nerve and muscle interactions and drug interventions.
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Neuromuscular
Junction Nerve Vs
Muscle
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Table of Contents
MAIN BODY...................................................................................................................................1
PART 1............................................................................................................................................1
What receptors are expressed on the postsynaptic cell..........................................................1
What is required for neurotransmission to occur at the muscle.............................................1
Requirements for muscle transaction.....................................................................................2
PART 2............................................................................................................................................7
What happens and why...........................................................................................................7
Comparison of effects.............................................................................................................7
PART 3............................................................................................................................................9
Dose Response Curve Suxamenthonium................................................................................9
Suxamenthonium..................................................................................................................10
REFERENCES..............................................................................................................................14
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MAIN BODY
PART 1
What receptors are expressed on the postsynaptic cell
Postsynaptic receptors are mainly binds with Neurotransmitter. In Postsynaptic cell, this
Neurotransmitter receives signals that trigger electric signals by regulating all activities of ion
channels. There are several glutamate receptors in which some receptors play an important role
on postsynaptic cell including: NMDA, AMPA and kainite receptors (Limanaqi and et. al.,
2020). Glutamate receptors which are one of the important receptors found on the postsynaptic
cell exist primarily in central nervous system and dendrites of post synaptic cell. Both Ion tropic
and metabotropic glutamate receptors can open in response to glutamate. These both cause cells
postsynaptic cell to get 2nd messengers in order to regulate all gene expressions and then
accordingly release neuroactive compounds.
In addition, in the context of the main receptors glutamate receptors, it can be said that the
type of L- glutamate receptors, plays an important role as it is present on the postsynaptic cell. It
is the excitatory neurotransmitter in the mammalian CN. It does not act individually as it requires
2 modes via it acts such as: ligand gated ion channels and G protein coupled receptors. It is main
primary mediator of excitatory transmission and it is one of the main elements which allow us in
learning something and memorizing. So, from this it can be said that this receptor is prominent in
the human body where one of the brain's main neurotransmitter are present.
What is required for neurotransmission to occur at the muscle
In the context of neurotransmission, it can be said that acetylcholine molecule plays an important
role in presenting or occurring neurotransmission at the muscle (Fogarty, Sieck and
Brandenburg, 2020). This Acetylcholine, which is known as a small molecule act as a chemical
messenger for propagating nerve impulses in between nerve and muscle at neuromuscular
junction. For occurring neurotransmission at the muscle there is requirement of focusing on all
main 4 stages which makes this process complete such as: synthesis and storage, release,
postsynaptic receptors and change. In the first stage of this process, there is a depolarization of
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the terminal membrane and then activation of voltage-gated channels. In next stages it changes in
the conformation of docking proteins.
So, it can be said that this neuromuscular junction is a chemical synapse between muscle fibre
and motor neuron. This junction plays an important role in neurotransmission as for transmitting
a signal it allows the motor neuron to the muscle fibre. When an AP occurs then range or amount
of neurotransmitter increases and it releases in nerves innervating skeletal muscles. The main
characteristic of small molecule and synaptic junction in the process of neurotransmission is
there is a distinct separation between postsynaptic and presynaptic membrane and the space
between both synaptic tell us that there is an intermediary signalling mechanism.
Requirements for muscle transaction
There is requirement of mainly 3 things for muscle contraction and muscle transaction such as:
There is requirement of neural stimulus, there must be calcium in muscle cells for better
transaction and ATP is also required for providing energy to muscle. So, from this it can clearly
be said that calcium ions play an important role as muscle contraction and transaction cycle is
triggered by calcium ions which binds to protein complex troponin (Maggio and et. al., 2019).
Both Na2+ and Ca2+ are required in muscle transaction and contraction for membrane
depolarisation. It makes all Ions to move through membrane and leads to effective and proper
impulsive muscle transaction. There are some steps by which muscle contraction and
requirement for muscle contraction or transaction can be known in a detailed manner such as:
generation of action potential, Ca2 released, bonding of Ca2 with troponin then myosin cross
bridges attach and detach. After those muscles started contracting then Ca2+ removed which
shifts active filaments to its original position. So, from these all steps of muscle contraction it can
be said that calcium Ions or Ca2+ is one of the important element which provides element and
elasticity in this process.
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In the presence of neuromuscular drug, taking intensity of Transmission at 1098.2s, using
simulation it has been analysed that it produces a minimum contraction or twitch in nerves.
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While, repeating stimulation estimated to T = 655.0s, it increases twitches or nerve contraction
relatively more.
By directly stimulating the nerve through cholinergic transmission at neuromuscular junction,
with more transmission i.e. 2463.6 sec, then it will indirectly evoke the nerves contraction or
twitches.
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It has been analysed by reading this lab report description that neuromuscular drug that
causes a dose-dependent reduction, results in directly evoked the twitches i.e. muscle
contraction.
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On comparing the responses of nerve twitches and muscle twitches, it has evaluated that by
running stimulation test that muscle contraction is directly evoked relatively more with reduction
in nerve contraction, to produce muscle relaxation during treatment.
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In addition, it can be said that muscle contraction happens when an action potential
travels along the nerves to muscles. So, muscle contraction or transaction mainly starts when
nervous system generates a signal. This signal is called as an action potential which travels via
nerve cell and this nerve cell is called or known as motor neuron. So, overall it can be said that
nervous system and Ca2+ are important for this process.
PART 2
What happens and why
The effects of neostigmine and adrenaline-induced neostigmine on reactivation of the
rodent segmented hemi diaphragm upon stimulation of the phrenic nerve are reported.
Neostigmine extended the reaction: a noticeable increase occurred in a group of 6.4 x W ~ 7 mol
liter'. At more concentrated concentrations of neostigmine, the reactivity was reduced.
Adrenaline without neostigmine showed no significant change in the response to withdrawal.
However, further expansion occurred within the neostigmine vision and was mainly achieved in
the adrenal vision 3.2 x 10 ~ 7 - 1.3x 10-6 mol liters'1. Adrenaline 4.0 x 10 ~ * -1.3 x 10- * mol
liter-1 with neostigmine 4.0 x 70 - * - 6.4 x 10 ~ 7 mol liter-1 bar neuromuscular induced
tubocurarine more susceptible than neostigmine by alone (P <0.001). Epinephrine appeared to
enhance the anti-neostigmine effect by increasing the release of acetylcholine and improving the
reactivity of the post junctional acetylcholine receptor.
Comparison of effects
Neostigmine alone:
Both intravenous and PE-controlled neostigmine (0.2–66.7 μg / kg) expanded the caecal
samples to suboptimal proportions. For both the lower and upper extremities, plasma secretion of
neostigmine was similar after both methods of administration, while a higher incontinence rate of
20 μg / kg after intravenous administration was observed as a contrast (Aubertin-Leheudre and
et. al., 2019). and the electroporation course. The contractual views were not significantly
different after the two organizational courses.
Neostigmine increased caecal concentrations after both intravenous and transdermal EP
organization. The estimated ED50 estimate for neostigmine was approximately twice that of the
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iv group compared with the PE course. In any case, this separation of facts is not very great. The
worst increase observed in tension was only 20% less after the organization of the PE than after
the intravenous treatment. The contractile caecal reactions to neostigmine or intravenously
regulated PE did not completely change in the target dose (0.2–66.7 μg / kg). The caecal smooth
muscle showed no response to stimulation to PE without neostigmine.
The findings suggest that neostigmine delivered by electroporation stimulates activity
similar to that observed after intravenous organization both in time and in strength.
Electrification allows even lower dosages of water-soluble mixtures to be administered through
the skin, which is very promising for clinical use.
1μM and 10 μM tuborcurarine:
The effect of tubocurarine on endplate flow amplitudes was investigated in the light of
strong stimulation trains (50-150 / sec) in rebounding muscle splints, in the mouse and in the
torso. In rodents and mouse muscles, the presence of tubocurarine induced a more rapid (one
hour) decrease in the amplitudes of progressive platelet flow during stimulation trains. In the
frog, tubocurarine caused an increase in the apparent relief of normal platelet amplitudes during
the first phase of tedious pacing drive forces; this extension was followed by a quicker summary
of the abundance of conventional plates (Mech and et. al., 2020). These effects of tubocurarine
appear to be extremely rare due to insufficient control of its ability to encapsulate itself in
voltage circuits. The more rapid summary during the end plate flow trains in a tubocurarine view
showed poor mixing with coverage capability, indicating that a tension channel bar with
tubocurarine as the primary position did not contribute to the retrospective. The effect of
tubocurarine on apparent relief and on the summary of normal platelet amplitudes was usually
reduced by reducing recirculation. These results suggest that tubocurarine affects the
transmission of transmission at neuromuscular crossings during stimulation.
A strong focus of D-tubocurarine that halved jumper reactions (meaning [interquartile
range]) was seven times higher in the hemi diaphragm than in EDL (1.82 micron [1.43–2.20]
versus 0.26 micron [0.23- 0.29], P <0.01). Half of the average quantum content was higher in the
hemi diaphragm than in the EDL (0.57 [0.44–0.84] vs. (0.14 [0.11–0.19], P <0.01) The level of
[(125) I] alpha-bungarotoxin decreased. local restriction to nicotinic acetylcholine junction
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receptors is greater in the stomach than in EDL (1.15 fmol / mg [0.48–1.70] versus 0.55 fmol /
mg [0.23–0.70], P <0.05).
In individual musculoskeletal arrangements, encapsulation and synaptic capacity were
recorded at 22 ° C with intracellular microelectrodes loaded with 3 M KCl (8–12 Mω of
inhibition) using conventional strategies and the Axoclamp- 2A (Axon Instruments, City of
Union, CIRCA). The motor nerve of the unrelated neuromuscular arrangements was stimulated
by an attractive microelectrode transduced across the nerve, with heartbeats of 0.1 ms at 0.2 Hz
and a supramaximal voltage (constant 3–8 V) provided by a S-stimulus device. -44 (Grass
Instruments, West Warwick, RI) The signals were obtained and digitized by a 12-cycle A / D
inverter (Digidata 1200B, Axon Instruments). PC analysis was performed using a specially
designed set of electrophysiological analysis programs (Boehm and et. al., 2020). The average
quantum content (mo) of end plate capacities was determined in Krebs-Ringer low Ca2 + (0.4)
resolution mm), high Mg2 + (7.5 mm). The so-called “failure mechanism” 13 has been used
where mo = ln (NT / No), where NT talks about the total number of improvements passed to the
motor nerve and nor representation of the amount of delivery capacity (e.g. number of
improvements not followed by plaque capacity). To find out a single intersection, 100-150 zero
motor improvements were moved.
PART 3
Dose Response Curve Suxamenthonium
Suxamenthonium refers to a short acting medication and depolarising neuromuscular
blocking agent drug, given for producing the muscular relaxation to a patient during anaesthesia.
It mainly works to reduce intensity of muscle contractions in body, so, to measure how patient
responding towards dosage of this drug, an experiment has been conducted, whereby responses
of people are measured as per given dosage in following way -
Log Dose (M) Response (g)
Vmax / 2
(g)
2x10-7 0.1 30.15
5x10-7 0.3 30.15
1x10-6 0.4 30.15
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5x10-6 7.8 30.15
1x10-5 42.2 30.15
2x10-5 59.4 30.15
5x10-5 60.3 30.15
1x10-4 60.3 30.15
It has been interpreted through this response curve that intensity of muscle contractions is
reduced with increase in dosage of Suxamenthonium. However, in-take of less volume of this
drug i.e. from 2 x 10-7 to 1 x 10-6, no response has been seen. Therefore, to produce muscular
relaxation during anaesthesia, amount of suxamenthonium need to be increased slightly more.
Suxamenthonium
Reaction analyses:
The respiratory depression activity of suxamethonium chloride 02 mg / kg was achieved
with an increase in pulse and pulse. However, doses of suxamethonium chloride 0.4 mg / kg
provided comparable changes in cardiovascular and respiratory capacity (Fogarty and et. al.,
2019). These effects were not combined with cardiovascular arrhythmias, in which a significant
period of apnoea occurred.
The cardiovascular effects of suxamethonium in halothane anesthetized rodents
compromised something with propranolol and were completely suppressed with hexamethonium.
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