Lecture 1:
What is and makes electrokinetic transport (passive diffusion) possible?
Electrokinetic transport is possible because of the electrical gradient which is created by the
ions. We know that the concentration of potassium, K+ and protein anions, A- are higher
inside the cell than outside. The difference here is the potassium ions are able to move
outside the intracellular fluid by the help of a large quantity of potassium channels pumps.
Therefore there will be an outflux through the membrane by the positive ions while the
negative charge protein anions will remain inside the cell because of its low permeability
through the membrane (virtually non-existent).Making the negative proteins move closer to
the membrane. This momentum of
potassium out down the conc. gradient is
stopped when the negative charge which is
left behind and can’t follow the potassium
outflux tries to pull potassium ions back into
the cell. Do to this the potassium outflux
because equal to the potassium influx do to
the charge difference.
Meaning that the high permeability of
potassium ions and low permeability of
protein anions makes the charge of the cell
membrane from the inside negative in respect to the outside of the membrane, creating an
electrical gradient.
When the electrical gradient is created only during this period is the electrokinetic transport
possible. Since we know the inside of the membrane is negative and the outside is positive in
respect to the inside, this allows the flow of positive ions inside the cell (Na+, Ca+, K+)
while the negative ions outside the cell (Cl-, HCO3-).
Which ions will diffuse faster through the cell?
As we see from the picture the diffusion of Na+ and Ca++ will be
faster because both the diffusion and the conc. gradient and the
electrokinetic transport are directed to the same direction. While
the potassium ions and the negative charge ions will be slower
since the diffusion of ions with the conc. gradient is the opposite
to that of the electrical gradient of the electrokinetic transport.
How will the charge be distributed by an Na+ / K+ antiporter?
,Since this type of active transport is an asymmetrical one where 3 Na ions move out the cell
and only 2 K ions move in the cell will lead to a more positive charge outside of the cell in
respect to the inside.
How is a secondary active transport dependent on the primary active transport?
If we would block the primary active transport then the conc. of ions inside and outside the
cells are going to equilibrate. If the conc. equilibrate then the secondary active transport
protein, symport or antiport where one substance moves along the gradient will stop its
movement since the concentration of the substance outside is equal to the inside. This will
stop the second molecule which is traveling against the conc. gradient from entering the cell.
How is calcium - calmodulin complex generated?
When signal comes to the cell it will help open calcium channels in the cell membrane or in
smooth ER, which will release calcium ions into the cytoplasm
and increase the conc. of the calcium. The channel type of the
calcium channels depends on the stimulus. If it is an impulse
which is transmitted along the cell membrane then it is a voltage
gated channel. If it is a hormone or neurotransmitter binding to the
channel protein → ligand gated channel. If it is deformation of
cell membrane for ex. stretching it will be a deformation gated
calcium channel. Inside the cell we have calcium binding protein,
one of them is calmodulin, which has four calcium binding sites.
So when calcium conc. increases it binds calcium ions and
becomes activated. When this complex is active it will in turn
activate calcium calmodulin dependent protein kinase (CaMK),
which is able to activate certain cell function ex. certain channels,
proteins or transfer information to the nucleus and activating
certain DNA strands for transcription and translation.
How is secondary messenger cAMP generated?
A hormone or neurotransmitter binds to a receptor which activates a G stimulating protein
which further activates adenylyl cyclase in the cell membrane. This enzyme is able to convert
ATP into cAMP. The ATP energy is not liberated but instead used to make cAMP. cAMP is
able therefore to activate protein kinase A. A protein which is able
to phosphorylate certain proteins in the cell and change their
activity, such as pump activity or channel activity or even
intracellular proteins which transfer information farther to the
other substrate inside the cell.
, Ex. of such a mechanism is epinephrine if it binds to the beta one receptor in the heart. Which
leads to the activation of cAMP and thus to faster and harder contraction of cardiac muscle.
In our cells we also have a receptor which when bound by certain hormones or
neurotransmitters can activate inhibitory G protein and inhibit the adenylyl cyclase.
Ex. acetylcholine in the heart when bound to M2 receptor and inhibit adenylyl cyclase
function and inhibit heart activity.
How is the secondary messenger cGMP generated?
In some receptors we have receptors which in their intercellular part has a guanylyl cyclase
domain. So when a substance binds to a receptor the guanylyl cyclase becomes active and is
able to convert GTP into cGMP. The active cGMp is able to activate protein kinase G, which
is also able to open and close certain channels and activate
certain proteins.
Ex. of such a case is when ANP, atrial natriuretic peptide is
bound to such a receptor and causes blood vessel dilation.
We also have soluble guanylyl cyclase which is not
associated with the membrane. There could be substances
which diffuse into the cell such as nitric oxide which binds
to the soluble guanylyl cyclase and activates the enzymes
→ performing the same function as described earlier.
How does the system of IP3 and DAG work?
If a substance binds to a receptor, the G protein is coupled
to the phospholipase C activation. This enzyme uses PIP2
which is cleaved into two second messengers DAG and
IP3. The DAG activates protein kinase C which is able to
activate certain channels or activity of protein inside the
cell. The IP3 instead has its calcium channel receptor
located in the smooth ER. If IP3 binds to this channel,
calcium ions will be released from smooth ER. So if the
conc. of Ca ions increases in the smooth muscle cell it
will lead to contraction, in secretory cell → secretion and
in nerve cell → activation.
How does the eicosanoids system work?
For example, glutamate binds to the receptor it can
activate G protein which is coupled with the activation
of phospholipase A. This enzyme uses phospholipids
to generate arachidonic acid. This acid has two
What is and makes electrokinetic transport (passive diffusion) possible?
Electrokinetic transport is possible because of the electrical gradient which is created by the
ions. We know that the concentration of potassium, K+ and protein anions, A- are higher
inside the cell than outside. The difference here is the potassium ions are able to move
outside the intracellular fluid by the help of a large quantity of potassium channels pumps.
Therefore there will be an outflux through the membrane by the positive ions while the
negative charge protein anions will remain inside the cell because of its low permeability
through the membrane (virtually non-existent).Making the negative proteins move closer to
the membrane. This momentum of
potassium out down the conc. gradient is
stopped when the negative charge which is
left behind and can’t follow the potassium
outflux tries to pull potassium ions back into
the cell. Do to this the potassium outflux
because equal to the potassium influx do to
the charge difference.
Meaning that the high permeability of
potassium ions and low permeability of
protein anions makes the charge of the cell
membrane from the inside negative in respect to the outside of the membrane, creating an
electrical gradient.
When the electrical gradient is created only during this period is the electrokinetic transport
possible. Since we know the inside of the membrane is negative and the outside is positive in
respect to the inside, this allows the flow of positive ions inside the cell (Na+, Ca+, K+)
while the negative ions outside the cell (Cl-, HCO3-).
Which ions will diffuse faster through the cell?
As we see from the picture the diffusion of Na+ and Ca++ will be
faster because both the diffusion and the conc. gradient and the
electrokinetic transport are directed to the same direction. While
the potassium ions and the negative charge ions will be slower
since the diffusion of ions with the conc. gradient is the opposite
to that of the electrical gradient of the electrokinetic transport.
How will the charge be distributed by an Na+ / K+ antiporter?
,Since this type of active transport is an asymmetrical one where 3 Na ions move out the cell
and only 2 K ions move in the cell will lead to a more positive charge outside of the cell in
respect to the inside.
How is a secondary active transport dependent on the primary active transport?
If we would block the primary active transport then the conc. of ions inside and outside the
cells are going to equilibrate. If the conc. equilibrate then the secondary active transport
protein, symport or antiport where one substance moves along the gradient will stop its
movement since the concentration of the substance outside is equal to the inside. This will
stop the second molecule which is traveling against the conc. gradient from entering the cell.
How is calcium - calmodulin complex generated?
When signal comes to the cell it will help open calcium channels in the cell membrane or in
smooth ER, which will release calcium ions into the cytoplasm
and increase the conc. of the calcium. The channel type of the
calcium channels depends on the stimulus. If it is an impulse
which is transmitted along the cell membrane then it is a voltage
gated channel. If it is a hormone or neurotransmitter binding to the
channel protein → ligand gated channel. If it is deformation of
cell membrane for ex. stretching it will be a deformation gated
calcium channel. Inside the cell we have calcium binding protein,
one of them is calmodulin, which has four calcium binding sites.
So when calcium conc. increases it binds calcium ions and
becomes activated. When this complex is active it will in turn
activate calcium calmodulin dependent protein kinase (CaMK),
which is able to activate certain cell function ex. certain channels,
proteins or transfer information to the nucleus and activating
certain DNA strands for transcription and translation.
How is secondary messenger cAMP generated?
A hormone or neurotransmitter binds to a receptor which activates a G stimulating protein
which further activates adenylyl cyclase in the cell membrane. This enzyme is able to convert
ATP into cAMP. The ATP energy is not liberated but instead used to make cAMP. cAMP is
able therefore to activate protein kinase A. A protein which is able
to phosphorylate certain proteins in the cell and change their
activity, such as pump activity or channel activity or even
intracellular proteins which transfer information farther to the
other substrate inside the cell.
, Ex. of such a mechanism is epinephrine if it binds to the beta one receptor in the heart. Which
leads to the activation of cAMP and thus to faster and harder contraction of cardiac muscle.
In our cells we also have a receptor which when bound by certain hormones or
neurotransmitters can activate inhibitory G protein and inhibit the adenylyl cyclase.
Ex. acetylcholine in the heart when bound to M2 receptor and inhibit adenylyl cyclase
function and inhibit heart activity.
How is the secondary messenger cGMP generated?
In some receptors we have receptors which in their intercellular part has a guanylyl cyclase
domain. So when a substance binds to a receptor the guanylyl cyclase becomes active and is
able to convert GTP into cGMP. The active cGMp is able to activate protein kinase G, which
is also able to open and close certain channels and activate
certain proteins.
Ex. of such a case is when ANP, atrial natriuretic peptide is
bound to such a receptor and causes blood vessel dilation.
We also have soluble guanylyl cyclase which is not
associated with the membrane. There could be substances
which diffuse into the cell such as nitric oxide which binds
to the soluble guanylyl cyclase and activates the enzymes
→ performing the same function as described earlier.
How does the system of IP3 and DAG work?
If a substance binds to a receptor, the G protein is coupled
to the phospholipase C activation. This enzyme uses PIP2
which is cleaved into two second messengers DAG and
IP3. The DAG activates protein kinase C which is able to
activate certain channels or activity of protein inside the
cell. The IP3 instead has its calcium channel receptor
located in the smooth ER. If IP3 binds to this channel,
calcium ions will be released from smooth ER. So if the
conc. of Ca ions increases in the smooth muscle cell it
will lead to contraction, in secretory cell → secretion and
in nerve cell → activation.
How does the eicosanoids system work?
For example, glutamate binds to the receptor it can
activate G protein which is coupled with the activation
of phospholipase A. This enzyme uses phospholipids
to generate arachidonic acid. This acid has two
