Cells Flashcards
(transport, communication & signaling)
Which is easier to transport across cell membrane?
Glucose, H20, Na+, Steroid hormones, O2
(easiest to hardest)
O2, steroid, H2O, glucose, Na+
What are 2 types of passive transport?
Simple diffusion & Facilitated diffusion
What are 2 types of active transport?
Primary (direct) & Secondary (indirect)
What 2 factors can determine level of transport into a cell?
Concentration gradient & voltage gradient
What type of charged ion is more likely to be able to enter a cell?
positively charged ion
What type of solute can move straight through the lipid bilayer?
UNCHARGED hydrophobic solutes
What is an example of a uncharged hydrophobic solute?
CO2
Describe “Jx = Px ([X] - [x]o)”
Flux = Permeability x difference in concentration (between ECF & ICF)
What is required to transport hydrophilic solutes?
Transmembrane proteins
Describe the structure of integral membrane proteins (3 points)
- a-helical domains
- can pass through membrane multiple times
- Termini (end) may be cytoplasmic or extracellular
What are 4 types of transmembrane proteins?
- Pore (non-gated channels)
- Channel (gated pore)
- Carrier
- Pump (subtype of carrier)
What is the use of transmembrane proteins?
Provide solutes with a ‘solute permeation pathway’
Describe the hydrophilic permeation pathway created by transmembrane proteins.
Made up of amphipathic helices - alternating hydrophobic amino acids.
- hydrophobic surfaces face the lipid membrane
- hydrophilic surfaces create a central pore
What type of transport do pores allow?
Passive transport
What is the driving force for movement in pores?
Electrochemical gradient
Describe the properties of pores (2 points)
- always open
- multiple subunits
What is an exampled of a pore?
Aquaporins
What do channels allow for?
Facilitated diffusion
What is the driving force for movement in channels?
Electrochemical gradient
Describe the properties of channels (2 points)
- gated ion channel
multiple subunits
What is an example of a channel?
Potassium channel
What are 3 types of channels?
(think gated)
- voltage-gated
- ligand-gated
- mechanical-gated
What are the 2 types of ligand-gated channels?
- Intracellular ligand
- Extracellular ligand
What 4 parts does a channel have?
- a moveable gate
- a sensor (can sense: voltage, ligand, mechanical)
- a selectivity filter
- an open channel pore
Do carriers have a continuous transmembrane path?
NO
Describe the time taken of Carrier-mediated facilitated diffusion vs normal diffusion.
Carrier-mediated facilitated diffusion is slower
Carrier-mediated facilitated diffusion can become saturated. What factors can limit the flux (Jx)? (2 Points)
- Number of carriers in the membrane
- Speed by which carrier can cycle through steps and become ready for next substance.
Briefly describe steps of Carrier-mediated facilitated diffusion
- Carrier open
- X binds at binding site
- Outer gate shuts (X is ‘occluded’ inside protein)
- Inner gate opens
- X enters inside of cell
- Inner gate closes (nothing is ‘occluded’)
What is the driving force for movement in carriers?
Electrochemical gradient
What do carriers use to mediate active transport? (3 things)
- Pumps
- Cotransporters
- Exchangers
Examples of substances travelling against their gradient
- ions for neural communication
- uptake of glucose
What is the difference between primary & secondary active transport?
Primary:
- uses pumps - driving force = chemical reaction e.g. ATP hydrolysis.
Secondary:
- uses cotransporters & exchangers - driving force = uphill movement one of solute with the downward movement of another solute.
Give an example of a pump
Na+ - K+ ATPase
What is the difference between cotransporters & exchangers?
Co-transporters - move solutes in same direction
Exchangers - move solutes in opposite direction
What is the common example that is often found to cause the movement of solutes using cotransporters & exchangers?
The inward Na+ electrochemical gradient
What is another name for cotransporter?
Symporters
What is another name for exchanger?
Antiporters
What did the discoveries into cell communication lead to?
Concepts of chemical mediators & receptors
What is pilocarpine? (2 effects)
Poison that:
- increases saliva secretion
- decreases heart rate
What drug can inhibit the action of pilocarpine?
Atropine
What was concluded after discovering that atropine inhibits the actions of pilocarpine?
They both must act on a common target.
Who discovered acetylcholine as a chemical mediator?
Otto Loewi & Henry Dale
What did Loewi discover about acetylcholine?
It is an agent used in the chemical transmission of nerve impulses (neurotransmission)
Briefly outline the steps to Loewi’s experiment (acetylcholine)
- Stimulate vagus nerve
- Collect fluid
- Inject into denervated heart
- Slowed heart rate
What is another phrase for chemical mediators?
Extracellular signal molecules
What are broad examples of chemical mediators?
Hormones & Neurotransmitters
Describe briefly the process of cell signaling
Chemical mediators bind to receptors on target cells. This initiates intracellular signals that alter cell behaviour through effector proteins.
What is signal transduction?
Process of converting an extracellular signal to an intracellular signal
What is a mediator?
A chemical, peptide or protein that conveys information from one cell to another.
When is a mediator released?
In response to a stimulus.
What is the purpose of having multiple receptors use similar transduction mechanisms?
Allows for coordinated responses & amplification of signaling.
What is the criteria that establishes a substance as a mediator? (3 Points)
- able to produce biological action within an appropriate time frame.
- application of authentic sample reproduces the biological effect.
- Inteference with synthesis, release or action ablates biological response.
What are the 5 main types of intercellular communication?
- Contact-dependent
- Paracrine
- Synaptic
- Endocrine
- Autocrine
Where can signals act?
- locally
- over long distances
What can signals vary in?
- Speed
- Selectivity
Describe autocrine communication
Releases and mediator that will act on itself.
Describe the range of contact-dependent communication
Shortest (literally in contact) with target cell.
Where is contact-dependent communication common? (2 Points)
Development & Immune responses
What is contact-dependent communication?
Where the signaling cell comes into direct contact with the target cell.
What is paracrine communication?
The release of mediators that act on other target cells locally.
Describe how mediators used in paracrine communication are stored
Either stored in in vesicles or synthesized on demand.
What are 3 examples of substances that use paracrine communications?
- histamines
- nitric oxide
- prostaglandins (eicosanoids)
What specialized structures are used in neuronal signaling
Synapses
Describe what type of cells synapses target
Specific target cells that can be short or long distances from the cell body
What are the chemical mediators used in neuronal communication called?
Neurotransmitters
What are 2 examples of neurotransmitters?
- acetylcholine
- noradrenaline
Where does acetylcholine & noradrenaline act on?
On the heart
Describe the speed of neuronal signaling
Fast
What is endocrine signaling?
Communication in which signaling mediators are secreted into bloodstream - hormones.
Describe the length and time of endocrine communication
Long distances and therefore very slow
Is endocrine communication specific?
No
What forms can hormones come in?
- a protein e.g. insulin
- amino acid derived e.g. epinephrine
- a steroid e.g. estradiol
What are 2 methods of chemical mediator synthesis?
- synthesis of smaller molecules regulated by specific molecules
- synthesis of peptides regulated by transcription
What are 2 types of chemical mediators?
- pre-formed mediators that are stored in vesicles & released by exocytosis (rapid)
- on-demand mediators, released by diffusion (slow)
What did early studies into neuromuscular junctions lead to the discovery of?
Existence of ‘packages’ of neurotransmitters.
What are the 2 parts of neuromuscular junctions?
motor nerves + skeletal muscle
How was the experiment into the quantal hypothesis (prediction of existence of vesicles) carried out??
Calcium was removed from a neuromuscular junction.
Other than removal of calcium, what other experiment was carried out to identify packages in neurons as vesicles?
The use of electron microscopy to view exocytosis.
How are neurotransmitter actions terminated?
- Enzymes (acetylcholinesterase at the cholinergic synapse breaks down acetylcholine).
- Uptake of neurotransmitters back into the neurone (or supporting cells e.g. glia)
What is a ligand?
A molecule that binds to a receptor (may be an agonist or antagonist).
What is an endogenous agonist?
Chemical mediators, from WITHIN the body, that PRODUCE a response.
What are receptors?
Macromolecules that are recognition sites for neurotransmitters, hormones etc, that allow for cell-cell communication.
What is a benefit of knowing the function of a receptor?
Allows us to predict physiology.
How are receptors classified?
Based on structure into classes or superfamilies.
What are the types of receptors? (how many?)
4 receptors:
- ligand-gated ion channels (ionotropic receptors)
- G protein-coupled receptors (GPCR) (metabotropic receptors)
- Kinase-linked receptors
- Nuclear (intracellular) receptors
Ligand-gated, GPCR & Kinase receptors all have 3 common features - what are they?
- contain TRANSMEMBRANE segments (through hydrophobic amino acids)
- contain LIGAND-BINDING DOMAIN (usually extracellular)
- ligand are HYDROPHILIC (can’t cross cell membrane).
Describe the structure of nuclear receptors
- contain MULTIPLE DOMAINS
- ligand are HYDROPHOBIC (can cross cell membrane)
- acts as TRANSCRIPTION FACTORS.
What is an example of a nuclear receptor?
Steroid hormone receptors, including oestrogen receptors
What type of chemical mediator use ligand-gated ion channels & GPCR receptors?
Small molecules e.g. amino acid derived neurotransmitters.
What type of chemical mediator use GCPRs?
Peptide hormones
What type of chemical mediators use kinase-linked receptors?
Cytokines & peptide hormones
What type of chemical mediator uses nuclear receptors?
Steroidal hormones
What can occur as a result of the binding of a ligand?
A conformational change, leading to an intracellular signal or secondary messenger being generated.
Describe the times for the different receptors
Ligand-gated ion receptors - milliseconds.
GPCR - seconds
Kinase-linked receptors - hours
Nuclear receptors - hours
What are 4 cellular effects of receptor activation?
- Hyper-polarisation/depolarisation = electrical signals e.g. triggering exocytosis
- Ca2+ release = allows contractility & muscle movement
- Protein phosphorylation - changes in enzyme activity
- Protein synthesis - e.g. more channels inserted into the cell membrane.
Describe the brief structure of endogenous agonist
- 5 subunits (from a central aqueous pore)
What happens to a channel when there is an agonist binding?
Channel is open
What happens to a channel when an agonist is removed?
Channel closes
What are 2 ways a channel can become closed? (in reference to receptors)
- agonist is no longer bound
- receptor enters a ‘desensitized’ state.
How does the opening of a ligand-gated ion channel lead to excitation?
- the opening of a channel leads to an influx of ions into the cell.
- this changes the potential of the cell.
(activation of ionotropic receptors by excitatory neurotransmitters - membrane depolarization (more positive) - action potential firing)
What is a nAChR?
Nicotinic Acetylcholine receptor
Describe how the opening of ligand-gated channels can cause inhibition
- Activation of ionotropic receptors for inhibitory neurotransmitters
- membrane (hyper-polarisation)
- reduces action potential firing.
What is an example of a receptor which causes excitation?
nAChR (nicotinic acetylcholine receptor)
What is an example of a receptor which causes inhibition?
GABA
What makes ion channels specific to different ligand and ions?
The protein subunits make them different when being identified.
How many times does a GPCR span though a membrane?
7 times (7 transmembrane domains)
How do GPCR regulate effect proteins?
Via HETEROTRIMERIC GTP-binding protein
What is the heterotrimeric GTP-binding G protein made of?
- 1 alpha subunit
- 1 beta subunit
- 1 gamma subunit
How many types of G-proteins are there?
20
What are examples of effectors, whose function can be changed, as a result of G proteins?
- ion channels
- enzymes - adenylyl cyclase & phospholipase C (enzymes that are membrane bound)
What can modulate adenylyl cyclase?
G proteins
What stimulates an increase in Adenylyl cyclase?
Ga(s) - stimulators
Describe the process by which Ga(s) leads to an increase in PKA (protein kinase A)
Binding of Ga(s):
- increase in Adenylyl cyclase
- increase in cAMP
- increase in PKA
What causes an decrease in Adenylyl cyclase?
Ga(i) - inhibitory
Describe the process by which Ga(i) leads to a decrease in PKA (protein kinase A)
Binding of Ga(i):
- decrease in adenylyl cyclase
- decrease in cAMP
- decrease in PKA
What is cAMP
a secondary messenger
What is the role of Ga(q)?
Increases intracellular calcium through the enzyme phospholipase C
What subunit mediates Ga(s)?
alpha
What subunits mediates Ga(i)?
alpha, beta & gamma (only alpha involved in adenylyl cyclase inhibition)
What subunit mediates Ga(q)?
alpha
