Brain and behavior

B- Membrane proteins and specific functions of neuron

The neuron membrane contains certain transmembrane proteins that play a vital
role in specific nerve function.
Peripheral proteins will play a role of some receptors, they’ll give the identity for
the cell as belonging to the self so it won’t be attacked by the immune system.
The transmembrane proteins will play the role of channels like wells that will surf
to pass certain type of hydrophilic molecules (ex: ions) from side to side of the
cytoplasmic membrane.
On the one hand, two categories of molecules (transmembrane proteins) allow the
passage of ions across the membrane, either by active transport (protein pumps)
or passively (protein channels)

Use energy to
Proteins with actively transport
pores through the ions across the
center that allow membrane, but
certain ions to against their
flow down their concentration
electro chemical gradients.
and concentration
gradients

Concentration gradients: from regions of low concentration of some substances to

a region of a higher concentration.
When we speak about channels there’s two types, the first one will transport ions
passively  protein channels
The second one will actively transport the ions from side to side  ionic pumps or
protein pumps.
On the other hand, we have “The Protein Receptors” imbedded inside the
membrane, they will inform the neuron about the presence of the chemical
compound or chemical substances and messengers outside the cell (ex:
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neuromediators or hormones). They will receive the substances and will transmit
the message to the neuron by forming it about the kind of reaction or response it
should make immediately. .
Transmembrane proteins:
- Protein pumps: transport ions across the membrane by an active
mechanism that requires a supply of energy. The most common example
is the sodium-potassium pump (Na+ / K+) which maintains the sodium
and potassium level of the cytoplasm.
These pumps will hydrolyze the ATP and will be provided by energy,
this protein actively drives
the sodium outwards and the
potassium towards the
interior of the neuron.

The concentration of potassium K+ is

higher in the cytoplasm whereas the
concentration of the sodium Na+ is
much higher outside the cytoplasm.
So spontaneously, by physical law,
any substances will move from the
space where it’s highly concentrated to the place where it’s lightly concentrated.
So the movement will be passive.
That’s what we mean by concentration gradients, it will create a force that will
make the movement of substances from the highest concentration towards the
lowest concentration.
So if I want to push the substances from the lowest concentration medium to the
highest concentration medium (push them back), so I’m going against the current
or against the gradient of concentration. With this type of movement I need energy
to pump the substances towards the highest concentration space.
This energy is provided by the hydrolysis of cellular ATP (by cutting the liaison of
the phosphates and the adenosine) and release ADP+P energy that will be used to
fuel the pump and help it do its job. So they will push the potassium inside of the
cytoplasm and push the sodium outside the cytoplasm.
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So by this action, it will maintain

the equilibrium or concentration of
the sodium and potassium from both
side of the cytoplasmic membrane.
The channel isn’t a pump, so there’s
no need for energy, the substance
will move passively from the space
where it’ highly concentrated to the
place where it’s lightly
concentrated. For example the
potassium will move with or
accordingly to the concentration gradient, from the cytoplasm to the extracellular
milieu passively. Because it’s highly concentrated on the inside and slightly
concentrated on the outside.
- Ionic channels:
The protein channels are simple wells crossing the membrane and letting certain
ions pass through a passive transport that is to say not requiring energy.
The direction of the passage depends only on the forces exerted on the ions:
electrostatic force (when we have two difference in charges between two spaces,
the negatively charged space will attract the positively charged space, so it will
create a force of attraction which is called electrostatic force) and force related to
the differences of concentration.

electrostatic force when we have two difference in charges between two spaces,
the negatively charged space will attract the positively charged space, so it will
create a force of attraction which is called electrostatic force. When the potassium
moves to the extracellular space, positive charges are leaving the cytoplasm
towards the extracellular space, so they’ll leave behind them negative charges in
the cytoplasm and the extracellular space will be enriched with positive charges.

Because of the different gradient concentration force, this movement will create
another force opposite to the gradient concentration attraction the potassium back
to the negatively charged area (inside the cytoplasm).

This will create an equilibrium of movement of these potassium, going out and
coming back inside the cytoplasm.
The different channels are distinguished by
Their selectivity
Given that the channel
doesn’t let any ion pass.
Some aren’t very
selective. For example:
cationic channels that
are permeable to all
positive ions.
Other are permeable to
one or two types of ions
only. For example:
potassium channels that
let only K+ ions pass.
The chemo dependent
channels are connected
to receptors that will
catch the chemical
substance and will tell
or close, depending on
neuromediator.
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Their rule of opening
A channel may be in different
states, each characterized by
shape and permeability: open
closed, inactivated (i.e.
blocked) state.
For the so called voltage- For some, the opening the
dependent channels, the opening isn’t controlled by a
probability of opening is particular factor: they’re the
controlled by the escape channels that opens
electrical potential of the and closes in a purely random
neuron. (Opens when way.
they’ll detect a
modulation in the
The mechano-dependent
electrical potential of the
channels, the opening is
membrane of the neuron)
facilitated by a mechanical
deformation of the
The chemo-dependent cytoplasmic membrane
channels, the probability of (opens when the cytoplasmic
opening is controlled by the membrane is slightly pushed
presence of chemical mechanically)
messengers (neuromediators
or hormone) in the
extracellular space. the channel to open
the kind of
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That’s why all chemo dependent channels should be linked to a receptor. The
voltage dependent, the mechano dependent don’t need receptors but the chemo
dependent channels do need receptors.
- Receptors:
In order for the messenger molecules to exert control and give order to the chemo
dependent channels, they must first be specifically attached to membrane site of
the complementary shape, carried by the extracellular surface of the protein-
receptors.
So they should adapt perfectly to the receptor. Every receptor has a form or spatial
configuration that is perfectly complementary to the shape of the substance
This bond between complementary molecules has been compared to the adaptation
of a key to a lock.
So the binding of a hormone or neuromediator on its receptor will induce a
response of the neuron: the opening or closing of chemo dependent channels.
The coupling between receiver and channel can be more or less direct.

A- Ionotropic receptor: coupling is direct, the same protein is serving as

receptor and channel. I don’t need any intermediate between the receptor
and the channel because both are coming from the same protein. This
receptor channel has a receptor site on
its extracellular surface and well
which opens and allows the passage of
ions depending on the occupancy of
the receptor site (depending on the
neuromediator).

B- Metabotropic receptor: the channel is a completely different protein from

the receptor. In this case we speak about G (guanine) receptors linked
channel because we need a messenger between the receptor and the channel
to transmit the order to the channel.
The receptor and channel are coupled
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by a third messenger called G protein which is activated when the receptor

receives the chemical messenger.

Sometimes activated G protein influences the opening of the channel by a

strictly membrane process.
The G protein was linked to the receptor at the beginning, it was inactive we
call it GI, when the neuromediator will be linked to the receptor, the G
protein will be activated and move inside the membrane (a strictly
membrane process) towards the channel and give it directly the order to
open or close depending on the type of neuromediator.
This type of protein are called G protein dependent channels or G protein
dependent receptors

C- Metabotropic receptor:
In other cases G proteins in turn
activates a membrane enzyme in the
cytoplasmic membrane that catalyzes
the synthesis of a second messenger.
The second messenger circulating in
the cytoplasm will influence the channel
directly or indirectly (by a third
messenger).
When the G protein is activated by the receptor, instead of moving directly towards
the channel, it will stimulate a membrane enzyme.
When this enzyme is stimulated, this latter will create a second messenger from
some substances existing inside the cytoplasm that are called precursors (a
substance called A transformed to a product called B, the A is the precursor and
the B is the product). So the enzyme will transform, by catalyzing a chemical
reaction, a product that is called precursor to a product that is called second
messenger that will stimulate the channel.
So the mechanism is a membrane process followed by a cytoplasmic one via the
creation of a second messenger.
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In some cases the second messenger will stimulate another enzyme that will create
from a precursor a third messenger that will stimulate the channel. There could be
10 to 15 levels of messengers that could be created.
What’s important in this type of metabotropic receptor that the second messenger
will go to stimulate the channel.
You can imagine that in the first type of receptors the reaction is very quick, when
the receptor is occupied by the neuromediator, it will immediately activate the
channel because they’re the same protein, so there’s no time gap between the two
actions.
In the metabotropic receptors I need time because there’s the protein G that will
move towards the channel, so it’s not an immediate process, the reaction is slower.
On all our body, mind and any physiological reactions there’s 2 types the quick
reaction: ionotropic receptors produced between the nerve and the muscle
(touching something very hot quickly remove my hand) and the delayed
reaction: metabotropic receptors (pain from the burn or the gradual feelings that
come slowly after an injury) the pain is slowly to disappear because of the G
protein and the second messenger that are create and still inside the cytoplasm for a
minute, day, month, year or sometimes lifelong.
That’s why a baby experiencing a painful event for the first time, he’ll always
remember not to touch or create it again. This type of memory is due to the second,
third… messengers that are kept inside the cytoplasm and always evoke a reaction
at the level pf the brain reminding us about the accident. This is the base of
learning. All what we’ve learnt is an accumulation of messengers inside the
cytoplasm that will always work and some of the will modify the DNA in the
nucleus of the neuron that will create new receptors and new protein channels that
will always react at the level of the brain and corresponding exclusively to the
experimented events, trauma or learning process.
That’s why the neuron doesn’t reproduce. Because all the messengers will
disappear with the death of the previous neuron, so all the learning will disappear
immediately and we’ll start from 0 without any history.

B- Neuron at rest

The nerve messages are propagated in the form of electrical signals, which are
called the action potential.
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These action potentials means that when the neuron is stimulated.

But when it was at rest it has potential. It’s a transient change in the basic state of
the neuron: the resting potential.
So at any time, the neuron is electrically charged. At rest it has the resting
potential with a value of -70mv and when it’s activated we have this transient/brief
change of this basic state of resting potential. So we’ll pass to the positive side of
the polarization. So instead of having -70mv at rest, the neuron will reach the +50
or +54 mv when it’s activated.
Electrophysiological techniques (can measure that the neuron at rest is polarized,
“-” charged inside the cytoplasm and “+” charged outside the cytoplasm) have
shown that, like any cell, the inactive state neuron is polarized.
Its cytoplasm is at a negative potential with respect to the extracellular space, the
potential difference between the two spaces being several tens of millivolts -70mv
1- Bioelectric concepts
In the living matter, we don’t have wires inside the brain, there’s a conductive
space that is mainly the water, and we don’t have electrons like inert matter, but
we have ions that are atoms or molecules that have lost or gained electrons. In the
ma made electrical circuits like copper, the metal is a conductor, and the charged
particles are electrons not ions, but in living tissues the conductive spice isn’t
wires or metal but an aqueous solution containing water and positive or negative
ions.
Living matter is the
place of electrical
phenomena due, as
the inert matter, to
the distribution and
propagation in a
conductive milieu
of charged
particles.
In a man-made
electrical circuit the
conductor is usually metallic and the charged particles are electrons.
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In living tissues, the conductive milieu is an aqueous solution containing positive

and negative particles: ions.
The main ions involved the bioelectric phenomena are:

Sodium, potassium Chlorine anions

and calcium actions.
Negative ions derived
Positive ions derived from atoms having
from atoms that have acquired and electron.
lost their electrons
2- Ionic concentration in a neuron
The ions considered above have a very different concentration in the cells and in
the extracellular space.
This table makes it
to note that, with
respect to the outside,
the interior of the
neuron is rich in
potassium K+ and
poor in Sodium Na+
and in chlorine Cl-
that are very concentrated in the extracellular space. NaCl is a salt, so as every cell
in the organism, the extracellular space is always rich in salt, Sodium and Chlorine.
So taking a blood test, it will measure the ions in the extracellular space and not
inside the cells, that’s why sodium comes higher 140mmoles whereas the
potassium is lower 5mmoles and chlorine 100-150 mmoles.so in blood test we test
the quantity of electrolytes or ions in the extracellular space.
This is very important to measure because it reflects the electrical activity at the
level of the CNS and in some cases the psychiatric illnesses like anxiety or
depression… The imbalance of these ions can be the cause of the pathological
manifestation (low concentration of sodium, caused by low consummation of salt,
the electrical stimulation of the neuron could be disturbed and by consequence can
become disorientated, confused and depressed)
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It’s said that there exists for these ions a concentration gradient (difference of
concentration between the outside and the inside. So we can understand easily why
the sodium pass passively towards the cytoplasm and why potassium go out
passively of the cytoplasm same thing for the chlorine that goes passively inside
the cytoplasm
If we make the calculus or addition of “+” and “-” charges in the extracellular
space we notice that there’s electroneutrality (in the extracellular space I have the
same quantity of anions and cations) if I have +1 and -1 the result is 0 so if I have
the same quantity of cations and anions there’s an electroneutrality in the
extracellular space.
So the charges “+” and “-” are balanced in the extracellular milieu, there’s
electroneutrality.
If I make the addition or the sum of “+” and “-” charges in the cytoplasm we notice
that the + charges coming from potassium aren’t neutralized or balanced by the –
charges of chlorine. I have 14 chlorine and 14 sodium but 140 potassium so there
isn’t equivalent quantity of negative charges. The electroneutrality inside the
cytoplasm will be ensure by what will be called A- which are big molecules and
not ions, that are negatively charged, example like proteins that are a chain of
amino acids, and acid in an aqueous space will be ionized and will be charged
negatively that’s why these nucleic proteins and acids are charged negatively and
they’ll play the role of anions that will neutralize the quantity of positive charges
inside the cytoplasm. We call them the Organic anions.
In the neuron the “-” charges of the Cl- ions do not compensate for the “+” charges
of the Na+ and K+ ions, but the electroneutrality is ensured by the presence of
organic anions (A-), of varied negative charge, which include in particular,
proteins and nucleic acids.
That’s why
Between the two intracellular and extracellular spaces, no potential differences
should exist… at least if no communication existed between them because if the 2
spaces are neutral so I shouldn’t obtain potential difference between both but we
realized that by measuring the difference of potential through the membrane we
discovered that, even if it’s at rest, there is a difference of potential that is -70mv.
But we have seen that the cytoplasmic membrane separating them was provided
with ion channels permeable to certain ions. So if we had to think that there is
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electroneutrality from both sides of the cytoplasmic membrane this difference of

potential should not exist.
But it exists because there’s some channels that are all the time permeable inside
the cytoplasmic membrane even if a neuron is at rest. These channels are the
escape channels that will always break this electroneutrality from both sides.
So if I considered that the cytoplasmic membrane really doesn’t let anything pass
through it, I can imagine that the electroneutrality should exist and there’s no
potential difference in both sides. But because of the existence of these escape
channels there’s no electroneutrality and I’ll have potential difference from both
sides.