Chemical Signalling and Membrane Transport Flashcards
Physiology
First Messengers (4 types - explain)
- signalling molecules released from cells into the extracellular fluid, aim of affecting the functioning of other cells
- Neurotransmitters
- e.g. Acetylcholine
- These molecules are released from neurones to allow communication between excitable cells - Endocrine Hormones
- e.g. Insulin, Adrenaline
- These molecules are released from glands like the thyroid and adrenal glands and enter the blood stream to reach their target cells. - Paracrine Molecules
- e.g. NO from vascular endothelium
- Released paracrine molecules affect cells in close proximity - Autocrine Molecules
- e.g. Interleukin released from monocytes
- Autocrine molecules act on the cell type that has secreted it
Cells express protein molecules called receptors capable of recognising specific first messengers. When the first messenger combines with the receptor in order to modify activity in the target cell, we
refer to this as receptor activation. We refer to the first messenger which does this as an agonist. Receptors are usually membrane bound but some receptors are inside the cell.
When receptors are activated and the activity of intracellular molecules is modified to create a response, we refer to this as
signal transduction
Cell Receptors (explain)
The physiological effect of a first messenger can be different in different tissues.
For example, the first messenger and neurotransmitter, acetylcholine (Ach) affects cardiac and skeletal muscle differently.
Ach decreases cardiac muscle contraction but increases skeletal muscle contraction.
Even though there
are Ach receptors in both tissues, they are of different types.
Cardiac muscle expresses the muscarinic type of acetylcholine receptor and skeletal expresses the nicotinic type.
The existence of different receptor types is a widespread phenomenon among first messengers.
Activation of each receptor results in different cellular events occurring since they are linked to different subcellular effectors.
The nicotinic receptor is ion channel linked and the muscarinic receptor is referred to as G-protein linked.
As well as being classified according to the first messenger they are activated
by, receptors are also classified according to the type of effector they are associated with.
The two main types of receptors classified this way are ion channel linked and G-protein linked
Ion Channel Linked Receptors
These are membrane bound proteins which permit the movement of ions across the cell membrane.
When a receptor is linked
to an ion channel (which is referred to as a ligand gated channel), its activation causes the channel to open and ions to enter or leave the cell.
This can lead to changes in membrane potential (hyperpolarization or depolarization).
We have already mentioned the nicotinic receptor as an example of an ion channel linked receptor, this ion channel permits cations like Na+ and K+ through
G-Protein linked receptors and second messengers
G-proteins are membrane bound proteins whose job it is to recognise when their associated receptors are activated and pass that message on to the effector system that generates the physiological response.
They are essentially go between proteins linking receptor to effector.
They are called G-proteins because they associate with the molecules GTP (guanosine
triphosphate) when they are active and GDP (guanosine diphosphate) when they are inactive.
When activated, the G-protein
dissociates into subunits (the α subunit and βγ subunit) which can diffuse through the cell to affect ion channels or membrane bound enzymes.
When G-proteins affect enzyme activity they change the intracellular concentration of
chemicals referred to as second messengers. It is the second messengers which trigger the preprogrammed series of biochemical events within the cell and lead to the correct response.
To illustrate this consider the example of adrenaline (or
epinephrine to give it its US name) causing contraction of blood vessel smooth muscle, which can lead to an increase in blood pressure.
-> When adrenaline activates it’s G-protein linked receptor at the cell surface, the α subunit dissociates to increase activity of a membrane bound enzyme (phospholipase C).
-> This will increase production of the second messenger IP3 (Inositol triphosphate), IP3 activates a receptor on the surface of the sarcoplasmic reticulum and as a result calcium in released.
-> The increase in the concentration of calcium inside the cell is the trigger for the muscle to contract with more force.
-> When the muscle lining a blood vessel contracts with more force, the vessels diameter is reduced, which increases the pressure exerted
by blood against it’s walls
Passive Transport - Diffusion
Diffusion: the movement of molecules from an area where they are in high concentration to where they are in low concentration.
Factors affecting the rate of Diffusion:
- Size of concentration gradient
- Permeability of membrane to substance
- Surface area of membrane
- Molecular weight of the substance
- Distance over which substances diffuse
Passive Transport - Osmosis
This is a special case of diffusion, when water moves down its concentration gradient across a semi-permeable membrane, such as the cell membrane.
A solution with a water concentration different from that of normal body fluids can influence cell size via osmosis.
To illustrate this consider the red blood cell, if the water concentration of the plasma is lower than normal, water leaves the cell, causing the cell to shrink, when the water concentration is higher the cell
swells.
We refer to the ability of a solution to affect cell size in this way as tonicity.
Passive Transport - Facilitated Diffusion
This type of diffusion involves the movement of molecules down their concentration gradients (i.e. high to low concentration) but a membrane bound protein is necessary to facilitate their passage.
These carrier molecules combine with the substance to be transported, and this physical interaction causes the carrier to change shape and shift the position of that substance so that it crosses the membrane.
Glucose and amino acids are examples of substances transported in this way, being too large to cross the cell membrane by simple diffusion.
Active Transport
This is the transport of a substance across the cell membrane when ATP is used to fuel the process.
ATP is required since transport is against a substances concentration gradient (i.e. from a low concentration to a high one).
An example of an active
transporter is the Na+,K+ATPase (or Na+,K+ pump). This pump exchanges 3 Na+ ions for 2 K+ ions, moving Na+ out of the cell and K+ into it, which is against both their concentration gradients.
This is extremely important in maintaining cellular homeostasis and function.
Active transport directly using ATP in this way is referred to as primary (1o) active transport.
Secondary (2o) active transport takes advantage of the concentration gradient, which was established by the primary active transporter.
An example is that of
the Na+, glucose transporter expressed in the intestine, which transports glucose using the concentration gradient for Na+, created by the Na+, K+ATPase (i.e. the primary active transporter.
Vesicular transport is a type of active transport, please see anatomy lecture on Organelles for further information.
