Download PASSIVE TRANSPORT

The transport
through the
plasma membrane
LESSON NR. 10 - PSYCHOBIOLOGY
Diffusion, Osmosis and electrochemical gradient
The combination of a solute in a solution is gathered
through a process called DIFFUSION
For example, milk in tea or ink in water.
Role of the thermal agitation
Diffusion, Osmosis and electrochemical gradient
In DIFFUSION: At the beginning the molecules are all
concentrated in one point of the glass, and very rare or absent at
other points. With the passage of time, the number of molecules
(which move in a completely independent manner) which will tend
to move from the area with the highest concentration to the one
with the lowest concentration will be greater of the molecules
moving in the opposite direction.
This type of movement is defined according to the GRADIENT
OF CONCENTRATION and brings the solute in the liquid in a
BALANCE OF CONCENTRATION (No gradient).
The exact same phenomenon can also be observed in
two communicating vessels separated by a semipermeable membrane (i.e. that lets pass only a certain
type of molecules)
Diffusion, Osmosis and electrochemical gradient
OSMOSIS: It is a phenomenon in which there is a flow of solvent (usually water)
between two solutions separated by a semipermeable membrane; the phenomenon is
generally due to concentration differences, and in that case the solvent flows from the
less concentrated solution to the more concentrated until equilibrium is reached or
osmotic isotonicity
Diffusion, Osmosis and electrochemical gradient
ELECTROCHEMICAL GRADIENT: If the substance which
diffuses through the semi-permeable membrane is provided with
electric charge as are for example, the ION, the final condition of
balance will not only be influenced by concentration and then by
the gradient, but especially by electrostatic total forces that are
generated between the two compartments separated by the
membrane.
The transport through the plasma membrane
Now we must apply the concepts outlined above
to the plasma membrane, especially the one of
the neurons, and then we look at the main player
of the movement across the plasma membrane:
• The indoor and outdoor salt solutions
• The plasma membrane
• The trans-membrane proteins
The transport through the plasma membrane
Bearing in mind the ability of water to create a
shell of hydration around the polar molecules,
and thus having in mind that all free ions in the
intra- and extra-cellular water solutions are
hydrated ions. This feature gives the ions a
strong hydrophilicity and does not allow the latter
to pass through the hydrophobic wall of the
phospholipid bilayer, if not through the presence
in the special channels formed by the transmembrane protein membrane.
The transport through the plasma membrane
The transport through the plasma membrane can
then be of two types:
passive transport: transportation to the
concentration gradient, thus based on
DIFFUSION and therefore does not require
energy consumption
Active Transport: Transport AGAINST the
concentration gradient which therefore requires
the energy consumption
PASSIVE TRANSPORT
In passive transport, the transfer across the transmembrane of a substance:
1. Follows the concentration gradient of the
substance.
2. It reaches a final state of equilibrium characterized
by the equality of the substance concentrations in
the two compartments separated by the membrane.
3. In the particular case of the free ions and the
concentration of the molecules electrically charged
it depends on the balance over that electrochemical
equilibrium gradient.
4. It does not require an energy expenditure
It can be of two different types:
passive or simple diffusion
facilitated diffusion
PASSIVE TRANSPORT: simple diffusion
It represents the (rare) mode of entry / exit from the cell of all those molecules for which the
plasma membrane is not a barrier.
As passive transport, it only relies on the concentration gradient.
They are generally non-polar small molecules that are able to go into the spaces left by the
phospholipids: gaseous molecules (O2, CO2 and N2) or small hydrophobic molecules (benzene,
ammonia, glycerol, urea etc ...)
The membrane crossing speed in the
simple diffusion is directly proportional
to the lipid solubility of the molecule that
crosses it.
PASSIVE TRANSPORT: facilitated diffusion
It is the most common mode of entry / exit from the cell of sugars, amino acids, nucleosides and
free ions.
It involves typically polar molecules that in order to cross the phospholipid barrier must make use
of facilitation/mediation of suitable protein complexes (usually specific to various substances)
PASSIVE TRANSPORT: facilitated diffusion
These protein complexes bordering on both sides of the membrane can be
distinguished in protein-carrier or permease, and channel proteins
PASSIVE TRANSPORT: facilitated diffusion
The carrier proteins interact directly with the molecules of solute, recognizing in stereospecific manner the solute and thus forming the carrier-solute complex, which in turn
through conformational change permits the passage of molecules from one environment
to the plasma membrane.
They typically carries the metabolites and generic molecules. They can act sometimes
(with a right amount of energy) for the active transport
PASSIVE TRANSPORT: facilitated diffusion
The channel proteins interact with the solute in weaker way and allow the
passage of hydrophilic molecules through a pore whose opening and closing are
regulated through accurate and poly-specific mechanisms. Carrying more
typically ions, these are defined as ionic channels
PASSIVE TRANSPORT: facilitated diffusion
An important feature of facilitated diffusion is its saturability. In fact, while in the case of the
transported molecules by simple diffusion a concentration increment corresponds to the increase
of speed of transport, in the facilitated diffusion a concentration increment will lead to a certain
point to the saturation of the transport speed level.
PASSIVE TRANSPORT: facilitated diffusion
A particular case of facilitated diffusion is the one involving the water. In this case it is not the
solute to pass from one compartment to another, but the solvent. The passage of water occurs in
specific channels called aquaporins. These channels are so frequent within the membrane that
the speed of passage resembles that of a simple diffusion.
THE ACTIVE TRANSPORT
It is said active transport the transfer of a given molecule from the compartment
(intra- or extra-cellular) in which the substance has a lower concentration to he
one in which it has a higher concentration. Then in the opposite direction to the
gradient of concentration (or the electrochemical gradient in the case in which the
molecules are provided with electric charge).
This type of transport is defined as concentrative and always requires an energy
expenditure, and is then mediated by transporters.
Depending on the type of energy used by carriers we can distinguish:
Primary active transport  use of chemical energy and cleavage of ATP to ADP
Secondary active transport  use of alternative energies, eg. electrochemical
gradient for an ion
Active transport is the main mode of exchange through the membrane of many cell
metabolites (sugars, amino acids, nucleosides) but they can also take advantage
of passive transport.
Primary active transport  use of chemical energy and
cleavage of ATP to ADP
The transformation of ATP into ADP occurs in specific protein regions called ATP-Binding Cassette,
the presence of these sites involves the particular naming of these transporters: ABC.
Secondary active transport  use of alternative
energies, eg. electrochemical gradient for an ion
The glucose is
transported into the
cell through a
secondary active
transport (energy of
the electrochemical
gradient of Na +
ions)
ABSORPTION OF GLUCOSE in the
intestinal epithelium
The glucose is
transported out of
the cell through a
passive transport
by facilitated
diffusion
(mediated by
carrier proteins)
Secondary active transport  use of alternative
energies, eg. electrochemical gradient for an ion
In secondary active transport, we can distinguish:
Uniport: secondary carriage of one substance that moves
by exploiting the difference in electrochemical potential
created by the primary conveyor.
Co-transport is the simultaneous transport of two ionic
species or other solutes and can differentiate into:
•
Symport: uses the flow of a second solute gradient to
move another molecule against gradient with a
movement that takes place in the same direction. An
example is the glucose simportatore, that cotrasporta
second gradient two sodium ions for each molecule of
glucose imported into the cell
•
Antiport: is the simultaneous transport of two ionic
species or other solutes that move in different directions
through the membrane. One of the two substances is
left flowing second gradient, from a high-concentration
compartment to a low concentration. This generates the
entropic energy needed to drive the other solute against
gradient, from low to high concentration. A typical
example will be represented by the Na + / K +
ACTIVE TRANSPORT: endocytosis AND exocytosis
Endocytosis is an encapsulation of materials determined by the intervention of the membrane active process, which
changes its shape, surrounding the material to be introduced, and then enclose it in a vesicle that is free within the
cytoplasm.
The endocytosis requires considerable energy consumption and enables the intake of material with great size. If the
material is solid is called phagocytosis, pinocytosis if it is liquid. To take these materials the cell changes its shape,
emitting cytoplasmic extensions, called pseudopods, surrounding the material and enclose it in a vesicle,
constituted by a portion of the membrane, which is then free within the cell. Endocytosis is a process by which the
substances are incorporated into the cell within vesicles which are derived by the introversion of the membrane
towards the interior of the cell.
Exocytosis is the reverse process, by which the vesicles contained in the cytoplasm merge with the cell membrane,
thus releasing outside the cell to their contents. This process occurs, for example, in nerve cells
TRANSPORTERS IN THE MEMBRANE
Regardless of the different modes of transport set out above, all of the membrane transporters have
certain characteristics in common:
Are trans-membrane proteins that look out on both sides of the membrane
Present on their inner / outer portion of a specific recognition region of the single molecule, called
binding site
In consequence of the arrival of the molecule to be transported, the protein undergoes a
conformational change that allows the passage
A LITTLE TEST
Passive transport:
A. Passive diffusion
B. Facilitated diffusion
Active Transport:
D. Primary transport (against
gradient)
E. Secondary transport:
C. Uniport
E. Symport
Exocytosis / endocytosis:
F.-G. exocytosis
ION CHANNEL
Ion channels are protein systems that run through the
entire thickness of the plasma membrane and mediate
the PASSIVE transport of free ions by facilitated
diffusion.
They can be comprised of a single protein or by a
multi-protein complex which includes several sub-units
(each indicated by a Greek letter).
The various sub-units form a protein complex that
interacts directly with the membrane lipids and has in
its interior an aqueous pore that opening on both sides
of the cell constitutes a passage or gate.
ION CHANNEL
Being passive transport, the channels can not influence
the direction of movement that will always be done
according to the concentration gradient, but it can regulate
the flow, depending on whether the channel is open or
closed.
Through these adjustments the ion channels may change
the difference of electric intra-and extra-cellular fillers,
which normally constitute the resting membrane potential.
In the nerve cells (or in general in excitable cells) they are
involved in the generation of action potentials (through the
passage of hundreds of millions of ions per sec.)
The importance of ion channels is finally proven by
diseases that result from their failure (channelopathies)
which may occur by genetic causes (cystic fibrosis,
idiopathic epilepsy, spinocerebellar ataxia etc) or toxic
causes (poisons or drugs)
ION CHANNEL
Ion channels as many other protein compounds can
exist with a large variety of isoforms, made of
alternatives polypeptide chains, that are originated
by post-translational modifications or through editing
of mRNAs.
This confers highly specific structural and functional
characteristics to a channel and / or its isoforms,
enabling the cell to obtain specialized functions for
the various molecular compounds.
ION CHANNEL
An important feature of ion channels is
their selectivity for a given ion or a given
type of ion (anions, cations).
This property depends on the structural
and electrostatic features, in the aqueous
pore. In fact, the mouth of the channel is
normally provided with a filter (or ring) of
selectivity, composed of amino acids with
positive or negative electric charge.
Other selectivity factors depend on the
size and structure of the aqueous pore,
as well as in the molecular mechanism of
ion transfer through the pore (Ion stripped
of the hydration shell)
ION CHANNEL
Another very important feature of ion channels refers to control of their opening. In fact, apart from
a few channels that are constantly open (resting or leak, respectively the Cl- and K +) channels are
normally in the closed mode and open only in the presence of an appropriate stimulus, remaining
open for a few msec. Immediately after the opening, many ion channels undergo another
conformational change which consists in the occlusion of the aqueous pore and in contemporary
inability to open up again, even in presence of the stimulus that normally determines the opening.
This inactive or refractory condition is usually maintained for a few msec, after which the ion
channel get back in closed mode.
ION CHANNEL
Since channels dedicated to the passage of the
same ion may have different structural
organizations, it is preferred to classify ion
channels according to the adjustment of their
opening mode.
Following these criteria the channels are grouped
into relatively homogeneous families of channels.
We can have:
Channels governed by the membrane potential
Channels regulated by ligand
Channels regulated by other means (mechanical
tension, light, etc ...)
Ionotropic receptors
• Channels governed by the membrane potential
They are also referred to as voltage-gated
channels or channels regulated by voltage.
They give to the excitable cells the ability to
vary in a few msec, the intracellular content
of electric charges as compared to the
outside.
The voltage-dependent channels are so
called because they open only when the cell
membrane potential reaches a certain
value, called threshold.
This type of channels has a high level of
selectivity for the ions or the type of ions
that pass through them.
• Channels governed by the membrane potential
These capabilities, depend on the channel structure,
which includes 4 domain of about 300-400 amino acids.
Each domain contains 6 different trans-membrane
segments (S1 to S6, in the secondary structure of alphahelices) which are arranged in a symmetrical manner so
as to form the tetramer that comprises the channel.
Of the 6 segments, s5 and s6 make up the opening of the
aqueous pore and between them there is a loop of about
20 amino acids which together with the other 3 loops,
forms the selectivity filter.
The segments s1 to s4 are formed by electrically charged
amino acids and form the voltage sensor.
Some channels may ultimately have other sub-feature
units that mediate very important phenomena for the
channel as its correct position on the plasma membrane