Case 1. Neurotransmission
What is action potential?
• Depolarization, repolarization and hyperpolarization
• Na+, K+, Cl-
• Na+/K+ pump
• Voltage difference between membranes
• Myelin sheets
• Nodes of Ravers
• Axons and dendrites
What does define a neurotransmitter?
• Stored and made in pre-synaptic membrane
• Affect the post-synaptic membrane
• Acetylcholine, nor acetylcholine, dopamine
• Inhibitor / excitatory
What do you know about the neurotransmitter receptor?
• Intracellular receptors: ion channel linked, G-protein linked, enzymatic linked
(tyrosine and kinase)
• Androgenic receptors and choline receptors (nicotine and muscarine)
Learning goals 1
• How does an action potential generate? And how is it propagated?
• What defines a neurotransmitter?
o How can they be classified?
• How does the life cycle of a neurotransmitter look like?
o Production, storage, release and clearance
• How is calcium concentration modified?
• What types of receptors do exist? (ionotropic vs metabotropic)
o Structures
o Functions
Literature
Fundamental neurosciences (3th edition)
1
,Repetition of course 1 and 2 - The structure of a neuron
There are three different types of neurons:
1. Sensory neurons which conduct impulses to the CNS
2. Motor neurons which conduct impulses from the CNS away
3. Intermediate neurons which concuct impulses in the CNS
There are many sorts of neurons which can be classified based on several characteristics.
There are uni-, bi- or multipolar neurons.
A neuron consists of a cell body which is called soma (or perikaryon) and some neurites.
The soma consists of several organelles.
There are two sorts of neurites:
1. Axons, they carry the action potentials further away from the soma. Thus, they carry
the output
2. Dendrites, they carry the action potentials to the soma. Thus, the carry the input
At the end of the axon, there is the axon terminal. This is the place where the axons get in
touch with the dendrites from the other neurons. The connection between the terminal
axon and the dendrites is called synapse.
At this axon terminal, there are a lot of synaptic vessels (neurotransmitters) which will be
released when there is an electrical stimulation (action potential). There are no
microtubules. There are a lot of mitochondria for active transport (for example).
The synapse consists of two sides: the presynaptic membrane of the axon and the
postsynaptic membrane of the dendrite. Between these two membranes lies the synaptic
cleft.
The neuron is covered by a neuronal membrane. The membrane consists of different
proteins that can carry out substances in and out of the neuron.
2
,A neuron’s shape is formed by the cytoskeleton which exists of: microtubules (formed out
of the protein tubulin), microfilaments (made out of actin) and neurofilaments
(intermediate filaments)
Neurons are accompanied by glial cells. In the case of the action potential, Schwann cells
and oligodendroglia play an important role. These two cells form myelin sheets over the
neurites of the neurons to fasten the conduction.
Learning goal 1.1 - How does an action potential generate? And how is it propagated?
(Literature: fundamental neuroscience chapter 5)
How does an action potential generate?
The cytosol in the neuron at rest is negatively charged with respect to the extracellular fluid.
The action potential is a rapid reversal of this situation such that, for an instant, the inside
of the membrane becomes positively charged with respect to the outside. The action
potential is also often called a spike, a nerve impulse, or a discharge. When the neuronal
membrane is at rest, the voltmeter reads a steady potential difference of about –65 mV
(resting potential). During the action potential, however, the membrane potential briefly
becomes positive and recovers later on.
The depolarization that causes action potentials arises in different ways in different
neurons. In most cells, each action potential is initiated in the initial portion of the axon,
known as the axon initial segment. The initial segment of the axon has the lowest threshold
for action potential generation because it typically contains a moderately high density of
Na+ channels that have a more negative activation threshold and it is a small compartment
that is easily depolarized by the in-rush of Na+ ions. Once a spike is initiated, this action
potential then propagates orthodromically down the axon to the synaptic terminals, where
it causes release of a neurotransmitter, as well as antidromically back through the cell body
and into the cell dendrites, where it can modulate intracellular processes.
3
, The first part, called the rising phase, is characterized by a rapid depolarization of the
membrane. This change in membrane potential continues until Vm reaches a peak value of
about 40 mV. The part of the action potential where the inside of the neuron is positively
charged with respect to the outside is called the overshoot. The falling phase of the action
potential is a rapid repolarization until the membrane is actually more negative than the
resting potential. The last part of the falling phase is called the undershoot, or after-
hyperpolarization. Finally, there is a gradual restoration of the resting potential. From
beginning to end, the action potential lasts about 2 milliseconds (msec). The critical level of
depolarization that must be crossed in order to trigger an action potential is called
threshold. The action potential is a ‘yes’ or ‘no’ reaction, there is no midway. Yes-reaction
when the trigger causes the membrane potential to become larger than the threshold level
or no reaction when the trigger does not cause the membrane potential to become larger
than the threshold level and there is no-reaction.
Action potential is caused when different ions cross the neuron membrane. A stimulus first
causes sodium channels to opens. Because there are many more sodium ions on the
outside, and the inside of the neuron is negative relative to the outside, the sodium ions
rush into neurons (rising phase).
1. In the resting state, the sodium and potassium channels are closed and the
membrane is charged negatively (around -65 mV). These gated channels open only
when an action potential trigger them (voltage channels).
2. Threshold. Threshold is the membrane potential at which enough voltage-gated
sodium channels open so that the relative ionic permeability of the membrane
favours sodium (Na+) over potassium (K+). Threshold is also called the critical level of
the depolarization. The depolarization can be causes by the influx of Na+ (these
steps) or the by injecting electrical current through a microelectrode (not described)
3. Rising phase. When the inside of the membrane has a negative electrical potential,
there is a large driving force on Na+ ions which rises the membrane potential to + 40
mV. Therefore, Na+ ions rush into the cell through the open sodium channels,
causing the membrane to rapidly depolarize.
4. Overshoot. Because the relative permeability of the membrane greatly favors
sodium, the membrane potential goes to a value close to ENa, which is greater than
0 mV.
4
What is action potential?
• Depolarization, repolarization and hyperpolarization
• Na+, K+, Cl-
• Na+/K+ pump
• Voltage difference between membranes
• Myelin sheets
• Nodes of Ravers
• Axons and dendrites
What does define a neurotransmitter?
• Stored and made in pre-synaptic membrane
• Affect the post-synaptic membrane
• Acetylcholine, nor acetylcholine, dopamine
• Inhibitor / excitatory
What do you know about the neurotransmitter receptor?
• Intracellular receptors: ion channel linked, G-protein linked, enzymatic linked
(tyrosine and kinase)
• Androgenic receptors and choline receptors (nicotine and muscarine)
Learning goals 1
• How does an action potential generate? And how is it propagated?
• What defines a neurotransmitter?
o How can they be classified?
• How does the life cycle of a neurotransmitter look like?
o Production, storage, release and clearance
• How is calcium concentration modified?
• What types of receptors do exist? (ionotropic vs metabotropic)
o Structures
o Functions
Literature
Fundamental neurosciences (3th edition)
1
,Repetition of course 1 and 2 - The structure of a neuron
There are three different types of neurons:
1. Sensory neurons which conduct impulses to the CNS
2. Motor neurons which conduct impulses from the CNS away
3. Intermediate neurons which concuct impulses in the CNS
There are many sorts of neurons which can be classified based on several characteristics.
There are uni-, bi- or multipolar neurons.
A neuron consists of a cell body which is called soma (or perikaryon) and some neurites.
The soma consists of several organelles.
There are two sorts of neurites:
1. Axons, they carry the action potentials further away from the soma. Thus, they carry
the output
2. Dendrites, they carry the action potentials to the soma. Thus, the carry the input
At the end of the axon, there is the axon terminal. This is the place where the axons get in
touch with the dendrites from the other neurons. The connection between the terminal
axon and the dendrites is called synapse.
At this axon terminal, there are a lot of synaptic vessels (neurotransmitters) which will be
released when there is an electrical stimulation (action potential). There are no
microtubules. There are a lot of mitochondria for active transport (for example).
The synapse consists of two sides: the presynaptic membrane of the axon and the
postsynaptic membrane of the dendrite. Between these two membranes lies the synaptic
cleft.
The neuron is covered by a neuronal membrane. The membrane consists of different
proteins that can carry out substances in and out of the neuron.
2
,A neuron’s shape is formed by the cytoskeleton which exists of: microtubules (formed out
of the protein tubulin), microfilaments (made out of actin) and neurofilaments
(intermediate filaments)
Neurons are accompanied by glial cells. In the case of the action potential, Schwann cells
and oligodendroglia play an important role. These two cells form myelin sheets over the
neurites of the neurons to fasten the conduction.
Learning goal 1.1 - How does an action potential generate? And how is it propagated?
(Literature: fundamental neuroscience chapter 5)
How does an action potential generate?
The cytosol in the neuron at rest is negatively charged with respect to the extracellular fluid.
The action potential is a rapid reversal of this situation such that, for an instant, the inside
of the membrane becomes positively charged with respect to the outside. The action
potential is also often called a spike, a nerve impulse, or a discharge. When the neuronal
membrane is at rest, the voltmeter reads a steady potential difference of about –65 mV
(resting potential). During the action potential, however, the membrane potential briefly
becomes positive and recovers later on.
The depolarization that causes action potentials arises in different ways in different
neurons. In most cells, each action potential is initiated in the initial portion of the axon,
known as the axon initial segment. The initial segment of the axon has the lowest threshold
for action potential generation because it typically contains a moderately high density of
Na+ channels that have a more negative activation threshold and it is a small compartment
that is easily depolarized by the in-rush of Na+ ions. Once a spike is initiated, this action
potential then propagates orthodromically down the axon to the synaptic terminals, where
it causes release of a neurotransmitter, as well as antidromically back through the cell body
and into the cell dendrites, where it can modulate intracellular processes.
3
, The first part, called the rising phase, is characterized by a rapid depolarization of the
membrane. This change in membrane potential continues until Vm reaches a peak value of
about 40 mV. The part of the action potential where the inside of the neuron is positively
charged with respect to the outside is called the overshoot. The falling phase of the action
potential is a rapid repolarization until the membrane is actually more negative than the
resting potential. The last part of the falling phase is called the undershoot, or after-
hyperpolarization. Finally, there is a gradual restoration of the resting potential. From
beginning to end, the action potential lasts about 2 milliseconds (msec). The critical level of
depolarization that must be crossed in order to trigger an action potential is called
threshold. The action potential is a ‘yes’ or ‘no’ reaction, there is no midway. Yes-reaction
when the trigger causes the membrane potential to become larger than the threshold level
or no reaction when the trigger does not cause the membrane potential to become larger
than the threshold level and there is no-reaction.
Action potential is caused when different ions cross the neuron membrane. A stimulus first
causes sodium channels to opens. Because there are many more sodium ions on the
outside, and the inside of the neuron is negative relative to the outside, the sodium ions
rush into neurons (rising phase).
1. In the resting state, the sodium and potassium channels are closed and the
membrane is charged negatively (around -65 mV). These gated channels open only
when an action potential trigger them (voltage channels).
2. Threshold. Threshold is the membrane potential at which enough voltage-gated
sodium channels open so that the relative ionic permeability of the membrane
favours sodium (Na+) over potassium (K+). Threshold is also called the critical level of
the depolarization. The depolarization can be causes by the influx of Na+ (these
steps) or the by injecting electrical current through a microelectrode (not described)
3. Rising phase. When the inside of the membrane has a negative electrical potential,
there is a large driving force on Na+ ions which rises the membrane potential to + 40
mV. Therefore, Na+ ions rush into the cell through the open sodium channels,
causing the membrane to rapidly depolarize.
4. Overshoot. Because the relative permeability of the membrane greatly favors
sodium, the membrane potential goes to a value close to ENa, which is greater than
0 mV.
4
