Neuromuscular and Interneuron Junction

There are two major types of synapse (1) the chemical synapse and (2) the electrical synapse

(1) The chemical synapses

- Almost all the synapses used for signal transmission in the CNS of the human being are
chemical synapse
- First neuron →secretes chemical substance called neurotransmitter/transmitter substance
in its nerve ending → act on receptor in the membrane of the next
neuron→excite/inhibit/modify neuron
- Neurotransmitter : acetylcholine, norepinephrine, epinephrine, histamine, gamma-
aminobutyric acid (GABA), glycine, serotonin, and glutamate.
- all skeletal neuromuscular junctions use only acetylcholine as the transmitter,
whereas synapses between neurons (interneuron junction) use a large number of
different transmitters
- Principle of “One-Way” Conduction : they always transmit the signals in one direction
From the neuron that secrete the neurotransmitter (presynaptic neuron) to the neuron on
which the transmitter acts (postsynaptic neuron)
- Presynaptic Terminals
 Presynaptic terminals : terminal knobs,
boutons, end-feet, or synaptic knobs
 The presynaptic terminal is separated
from the postsynaptic neuronal soma by
a synaptic cleft having a width usually of
200-300 angstroms.
 The terminal has 2 internal structures
important to excitatory or inhibitory
function of the synapse : transmitter
vesicle and mitochondria
 The transmitter vesicle : contain the
neurotransmitter →released to synaptic
cleft →excites or inhibits the postsynaptic
neuron (excite if the neuronal membrane
contains excitatory receptors, inhibits if
the membrane contains inhibitory receptors)
 The mitochondria : provide adenosine triphosphate (ATP) for supplies the energy
for synthesizing new neurotransmitter.
 Action potential spreads over a presynaptic terminal →depolarization of its
membrane →a small number of vesicles emptying, neurotransmitter into the
cleft→permeability changes of postsynaptic neuronal membrane→excitation or
inhibition of postsynaptic neuron, depend on the neuronal receptor.

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 - Mechanism by which an Action Potential Causes Transmitter Release from the Presynaptic
Terminal – Role of Calcium Ions
 Presynaptic membrane : contains large numbers of voltage-gated calcium channels.
 Action potential → depolarizes the presynaptic membrane →calcium channel open
and allow large numbers of calcium ions to flow into the terminal→bind with special
protein molecules on the inside surface of the presynaptic membrane, called release
sites → release sites open through the membrane → allow transmitter vesicle to
release transmitter into the cleft(exocytosis).
 The quantity of neurotransmitter that is then released is directly related to the
number of calcium ions that enter.
 For those vesicles that store acetylcholine(ACh), between 2000-10000 molecule ACh
are present in each vesicle
- Action of the Neurotransmitter on the Postsynaptic Neuron – Function of “Receptor
Proteins”
 The postsynaptic membrane contains large number of receptor protein that have 2
component : 1. a binding component : protrudes outward from membrane into cleft
2. an ionophore component →ion channel and “second messenger”
activator
 Ion Channel
Rapid effect
1. Cation channels : sodium (most often), potassium, calcium ions
Cation channels are lined with negative charges, these charges attract the
positively charge into the channel when the channel diameter increases.
Neurotransmitter that opens cation channel is called an excitatory transmitter
2. Anion channels : mainly chloride
Neurotransmitter that opens anion channel is called inhibitory transmitters
The channel usually opens within a fraction of a millisecond, if neurotransmitter
no longer present, the channel are blocked rapidly.
 “Second Messenger” System in the Postsynaptyc Neuron
Prolonged effect

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  G-protein

Alpha portion of the G-protein separates from the beta and gamma portions and then is
free to move within the cytoplasm of the cell, perform function depending on the specific
characteristic of each neuron :

1. Opening specific ion channels through the postsynaptic cell membrane

e.g potassium channel that is opened, often stays open for a prolonged time
2. Activation of cyclic adenosine monophosphate (cAMP) or cyclic guanosine
monophosphate (cGMP) in the neuronal cell
cAMP and cGMP can activate highly specific metabolic machinery in the neuron, can
initiate many chemical result→ long-term changes in cell structure, which in turn
alters long-term excitability of the neuron
3. Activation of one or more intracellular enzyme
Enzymes can cause any one of many specific chemical functions in the cell
4. Activation of gene transcription
Gene transcription → new formation of proteinswithin the neuron→changing its
metabolic machinery or its structure
- Excitatory or Inhibitory Receptors
Excitaton
1. Opening of sodium channels to allow large numbers of positive electrical charges to
flow to the interior of the postsynaptic cell. This raises the intracellular membrane
potential in the positive direction up toward the threshold level for excitation. It is by
far the most widely used means for causing excitation.
2. Depressed conduction through chloride or potassium channels, or both. This
decreases the diffusion of negatively charged chloride ions to the inside of the
postsynaptic neuron or decreases the diffusion of positively charged potassium ions to
the outside. In either instance, the effect is to make the internal membrane potential
more positive than normal, which is excitatory.
3. Various changes in the internal metabolism of the postsynaptic neuron to excite cell
activity or, in some instances, to increase the number ofexcitatory membrane
receptors or decrease the number of inhibitory membrane receptors.
Inhibition
1. Opening of chloride ion channels through the postsynaptic neuronal membrane. This
allows rapid diffusion of negatively charged chloride ions from outside the
postsynaptic neuron to the inside, thereby carrying negative charges inward and
increasing the negativity inside, which is inhibitory.
2. Increase in conductance of potassium ions out of the neuron. This allows positive ions
to diffuse to the exterior, which causes increased negativity inside the neuron; this is
inhibitory.
3. Activation of receptor enzymes that inhibit cellular metabolic functions that increase
the number of inhibitory synaptic receptors or decrease the number of excitatory
receptors.

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 - Chemical Subtances that function as Synaptic Transmitters

1. Small-Molecule, Rapidly Acting Transmitters

 The vesicles that store and release small-molecule transmitters are continually
recycled and used over and over again
 Vesicle→fuse to presynaptic membrane→open and release
neurotransmitter→vesicle become part of membrane→invaginates back to inside of
presynaptic terminal→pinches off to form a new vesicle
 E.g Acetylcholine(acetyl coenzyme A+choline) in the presence of enzyme choline
acetyltransferase→vesicle→release to cleft→acetylcholine rapidly split again to
acetate and choline by the enzyme cholinesterase in synaptic cleft→vesicles are

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 recycled in presynaptic terminal, choline transported back to be used again for
synthesis of new acetylcholine

Examples of Principal (Classic) Neurotransmitters

Neurotransmitter Function Receptor Ionic Location

Mechanism Mechanism
Acetylcholine Rapid Ion channel Opens cation (1)the terminals of the large
excitation channel (fast pyramidal cells from the motor
EPSP) cortex
(2)basal ganglia
(3)the motor neurons that innervate
the skeletal muscle
(4)the preganglionic neurons of the
autonomic nervous system
(5)the postganglionic neurons of the
parasympathetic nervous system
(6)some of the postganglionic
neurons of the sympathetic nervous
system
Main sensory and motor system
Norepinephrine Brain stem and hypothalamus

Glutamate Cerebral cortex

Nitric Oxide It is not stored in vesicle but instantly synthesized as needed and it diffuses from
presynaptic terminal to postsynaptic→changes intracellular metabolic function that
modify neuronal excitability for seconds, minutes, or even longer
Dopamine Rapid Opens anion Subtantia nigra
GABA inhibition channel for
chlorine (fast
IPSP)

Glycine
Serotonin Median raphe of the brain stem and
project to many brain and spinal
cords area especially to the
hypothalamus
2. Neuropeptide
 Not synthesized in presynaptic terminal, synthesized by ribosomes in the
neuronal cell body
 ribosome→RE→golgi apparatus : package the neuropeptide into vesicle and
released into cytoplasm, then transported to axon, traveling at the slow rate of
only a few centimeters per day
 some of actions include prolonged closure of calcium channel, prolonged
changes in the metabolic machinery of cells, prolonged changes in activation or

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 deactivation of specific genes in the cell nucleus, prolonged alteration in
number of excitatory or inhibitory receptor
(2) The electrical synapses
- Direct open fluid channels that conduct electricity from one cell to the next
- Consist of small protein tubular structure called gap junction that allow free movement of
ions from the interior of one cell to the interior of the next

Neuromuscular Junction

Neuromuscular Junction in Skeletal Muscle

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 - Skeletal muscle fibers are innervated by large, alpha myelinated nerve fibers derived from
large motor neurons in the anterior gray columns (horns) of the spinal cord or from the
motor nuclei of cranial nerves.it branches many times, the number of branches depends on
the size of the motor unit.
- A single branch that terminates on a muscle fiber at a site reffered as neuromuscular
junction or motor-end plate.
- On reaching the muscle fiber, the nerve loses its myelin sheath and breaks up into a number
of fine branches. Each branch ends as a naked axon and forms the neural element of the
motor end-plate. At the site of the motor end-plate, the surface of the muscle fiber is
elevated to form the muscular element/sole plate
- Junctional folds : to increase the surface area of the plasma membrane that lies to the
naked axon
- Synaptic cleft : filled with the basement membrane of the axon and muscle fiber
- Endoneurium : connective tissue sheath of the nerve fiber
- Endomysium :connective tissue sheath of the muscle fiber
- Nerve impulse (action potential) on reaching presynaptic membrane of the motor-end plate
→opening of voltage-gated Ca2+→allow Ca2+ enter the axon→stimulate fusion of vesicle on
presynaptic membrane→exocytosis→release ACh to cleft

Ach reach the nicotinic type of Ach receptors on the postsynaptic membrane→Ach-gated
channel are opened→postsynaptic membrane more permeable to Na+ions→Na+influx
→end-plate potential is created (local potential)

End-plate potential (if large enough)→Na+ channels opened →Na+ influx→Action potential
initiated and spread along the surface of sarcolemma→wave depolarization is carried into
muscle fiber to the contractile myofibrils through the system of T tubules→release of
Ca2+from sarcoplasmic reticulum → muscle contraction

Immediate hydrolysis of Ach by acetylcholinesterase (AChE) → Ach-gated channels closed →

muscle fiber repolarization

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