Biomed 2 - Cell communication0

What are membranes

Physical barriers impermeable to all things and substances

create different physical compartments between cells

What are the ways that cells signal

Intracellular signalling - between cellular compartments

Intercellular signalling - From cell to cell

Signalling from 1 to multiple cells - can be sent via blood/synapses

What are gap junctions

Cells communicate via gap junctions

Small gaps which allow small molecules to pass through 2 plasma membranes

How do signals cross membranes

Hydrophobically - free diffusion of gasses

hydrophilic - pumps, channels, vesicles, signalling molecules

How do signals cross membranes hydrophillically

Via pumps, which sit on the membrane and transport hydrophilic molecules to the other side of the membrane

Ion channels which allow ions/metals to pass at specific times

Vesicle fusion

Indirect signalling through receptors/pathways

How are signals released?

Constitutively - a cycle, flowing down the concentration gradient

Evoked - Only when a cell needs to evoke a signal - Gated channels open at specific times

What is free diffusion

Gases diffuse freely across the membrane - must be tightly controlled however gases are short lived

Ex of signalling molecules for it are steroids and gases

What is exocytosis and endocytosis

Endo - Molecules are digested by the membrane and brought into the cell

Exo - Signals packed into intracellular vesicles and released constitutively or evoked outside the plasma membrane

Ex. Proteins, peptides, amino acids, nucleotides

Examples of signalling molecules

Proteins, peptides, amino acids, nucleotides

What are the forms of signalling from secreted molecules

Paracrine, autocrine, synaptic, endocrine, gaseous signalling

What is paracrine signalling

Signal only affect cells in the immediate cellular environment

Very localised and limited to unicellular organisms

No diversity of signals due to receptor and signal being close in proximity

Terminate the signal by uptake into neighbouring cells, destruction by enzymes, sequestration by the extracellular matrix

What is autocrine signalling

Signal is released to the exact same type of cell = produces a higher concentration of signal compared to the single cell - boosts the signal, limited scope

What is synaptic signalling

Neurones are used to control complex multicellular organisms

What happens in neurons to activate action potentials

Information travels unidirectionally:

received in the dendrite » transduced along axon » transmitted to next neuron in the nerve terminals

Active dendrite = action potentials along the axon which reaches nerve terminals which secretes a neurotransmitters » transduces signal to another neuron

What are synaptic junctions

Ensure the signal is transmitted specifically and quickly

What is endocrine signalling

Secrete hormones into the blood

Specific - flows all around the body but only binds to its receptor

Huge diversity of signals/receptors

What is gaseous signalling

Released gases bypass the plasma membrane and directly activate enzymes inside the cell

Endocrine vs synaptic signalling

	Synaptic Signalling	Endocrine Signalling
Distance	The target is 100nm away from the release of the signal  - short distance	Targets anywhere in the body - long distance
Speed	Fast - take little time to reach the target	Slow - relies on diffusion to reach the target
Affinity of target	Low affinity receptors - signals are highly concentrated at the synapse	High affinity receptors - signals get diluted in the bloodstream so need high affinity receptors

What type of cells don’t need receptors

cells which use signalling via gap junctions or gases

What are receptors

Transmembrane protein located on surfaces of cells

Binding of the signal activates the receptor = production of intracellular signals

What are Ionotropic receptors

Allows for the flow of ions across membran

Opening of receptor allows passage of ions down gradient = changes membrane potential

Very selective

What are excitatory ionotropic receptors

High concentration of positive ions in the cell - depolarises the cell

Inhibitory ionotropic receptors

High concentration of negative ions in the cell - hyperpolarises the cells

What are metabotropic receptors

Generate new signals inside the cell (2nd messengers)

Indirectly regulate membrane bound proteins - signal doesn’t cross the membrane

Crosses through trimeric G proteins

What are trimeric G proteins

Intermediate between the receptor and target

has Alpha, beta, gamma subunit

Ligand binding = activates alpha subunit which binds to GTP = dissociation of B and G subunits which alter the activity of ion channels

This repeats in a constant loop

Baseline of metabotropic receptors

Neurotransmitter binds to its receptor » G-protein binds to receptor » activates enzyme » 2nd messenger activates > cascade » modifies ion channels

What are kinase receptors

Modify existing molecules to generate new signals

Usually enzymes/associated with enzymes

Ligand binds outside the cell = the kinase receptor amplifies signal inside the cell

What happens in kinase receptor pathways?

Ligand binds to kinase receptor » kinase phosphorylates itself by binding a Pi group which alters conformation of kinase to create a binding site to attract more Pi groups » further phosphorylation cascade of all enzymes

What are steroid receptors?

They’re located inside the cell to change gene expression by transcription

Activates transcription for gene expression, but attaches to the genes to create a protein = changed function

How to activate steroid receptors

Bind to DNA in the nucleus (before ligand binding) /cytoplasm (after)

Creates 2 responses:

A quick, small primary response

a slow, massive response

How fast are the receptors

Type	Description
Ionotropic	Very fast due to the high concentration gradient of ions on one side of the membrane + low concentration of ions on the other
Metabotropic	Relatively fast - speed is limited by the number of enzymatic reactions in the cell.
Kinase	Relatively fast - speed is limited by the many reactions it causes.
Steroid	Quite slow due to both primary and secondary responses. fast are the recep

The same signal can have multiple receptors…

1 signal can have multiple diverse effects - meaning the location of the receptor is important to the response

Even those int he same location can have different responses

Agonists vs antagonists

• Agonists bind to the receptor directly > activates the signal to mimic the signal that the ligand would make

• Antagonists bind to receptor indirectly or directly to block the signal/response of the ligand >> inhibits function of the receptors

Direct vs allosteric antagonism

Allosteric - binding at different site » conformational change so ligand cannot bind

Why is it important to know the structure of a drug?

Subtle changes to structure = change in function

What is a drug

it must produce a biological effect when given to a living organism

What is a medicine

A chemical preparation containing 1 or more drugs + other components (stabilisers, solvents)

What are biopharmaceuticals?

A wide range of medicinal products created by biological processes - usually involves recombinant DNA technology

Ex. vaccines, humanised monoclonal antibodies, hormones

Selectivity of drug action

Drug targets are extremely specific

Must have a selective action on a tissue

reflects specific expression patterns of protein drug targets

GOAL = low conc of the drug has high specificity to bind to the drug target (too much concentration = drug will bind to another receptor = bad)

What are the targets for drug action and where are they found?

Receptors, ion channels, enzymes, carrier molecules

They are found anchored in the cell membrane of cells

What decides the ability of drugs to work

Their ability to cross the cell membrane to get to targets within cells

What are receptors?

Proteins whose function is to recognise and response to chemical signals

Any target molecule with which a drug has to combine in order to elicit its specific side effect

What are ligands

Any drug that binds with high specificity to a molecular protein target

Ka = dissociation constant/association constant - equilibrium constant for the ligand

Kd = general equilibrium constant for the drug

What is Ka

The dissociation/association constant

What is Kd

A general equilibrium constant

smaller Kd means the drug binds with higher affinity

How do you get rid of agonist occupancy

Addition of an antagonist

Then increase agonist concentration to restore occupancy

What is an allosteric modulator

Positive - increased affinity for antagonist to bind/agonist to activate the receptor

Negative - binding will reduce the agonis’ts signal/efficacy

What happens when Ach (agonist) binds

Rotation of the outer subunit structure = opens channels