Cell signalling Flashcards
40% of all medications interact with what type of receptors?
GPCR
The majority of receptors are made up of
proteins
What are the two major categories of receptors
Transmembrane/cell surface receptors or cytoplasmic/nuclear receptors
Molecules that are very large or hydrophilic use what type of receptor?
Transmembrane/cell surface receptor
Small, hydrophobic molecules use what type of receptor?
Cytoplasmic or nuclear receptors
__________ binding changes the activites of the intracellular domains of the receptor, which initiates the response
Ligand
What are the four types of intracellular receptors?
(1) Ligand-gated ion channels
(2) GPCR
(3) Kinase-linked receptors
(4) Nuclear/cytoplasmic receptors
Name some examples of things that can act as singalling molecules/chemical messengers
proteins, peptides, sugars, lipid-derived molecules, hormones, cytokines, NT’s, pheromones, gaseous molecules
Signalling molecules that bind to and ACTIVATE receptors are called _______ or ________.
Agonists or ligands
Signalling molecules that bind to and INACTIVATE receptors are called ________ or _________.
Antagonists or blockers
The majority of intercellular signals are
Chemicals (NT’s, hormones)
What are the three types of intercellular signals?
(1) Chemicals
(2) Physical interconnections (tight junctions, gap junctions, desmosomes, etc)
(3) Gaseous
Intracellular signalling triggers activation of the receptor, which leads to…
A change in cellular behaviour
Different cells can respond differently to the same signal depending on:
(1) The sets of receptors the cell has
(2) The intracellular machinery
Why do drugs sometimes have unwanted side effects?
Because cells can respond differently to the same ligand
What are the 5 modes of extracellular signalling?
(1) Endocrine- long distance
(2) Paracrine
(3) Neuronal
(4) Autocrine
(5) Juxtacrine
What are the main types of signalling molecules used in endocrine signalling?
Hormones
Proteins, cytokines, histamine, and platelet-derived growth factor are examples of what type of signaling molecules?
Paracrine
How do cells communicate with one another using paracrine signalling?
The signals diffuse LOCALLY to neighbouring cells
Noradrenaline is an example of what type of signalling molecule?
Neuronal
Cytokine interleukin 1 monocytes are an example of what type of signalling molecule?
Autocrine
These cells secrete signalling molecules that bind to their own receptors to generate a change in their own behaviour
Autocrine
This type of signalling can be involved in positive or negative feedback
Autocrine
This type of signalling is CONTACT DEPENDANT. Immediate neighbours signal to each other via membrane bound molecules
Juxtacrine
Antigen presenting cells are an example of cells that use what type of signalling>
Juxtracrine
Communicating junctions and gap junctions are associated with what type of signalling?
Juxtacrine
What allows waves of electrical excitation to pass quickly through cardiac cells?
Gap junctions (juxtacrine signalling)
What type of signalling is involved in coordinating uterine contractions?
Juxtacrine
What are the three stages of intracellular communication?
(1) Reception
(2) Transduction
(3) Response
What happens in the first stage of intracellular communication- “reception?”
A chemical message binds to a protein on the cell surface
What happens in the second stage of intracellular communication- “transduction?”
The binding of the signal molecule alters the receptor. This starts a cascade of reactions
What happens in the third stage of intracellular communication- “response?”
The transduction pathway triggers a response (ie turning on a gene, activating an enzyme, rearranging the cytoskeleton, etc)
_________ activation leads to __________ signalling cascades and __________ messenger systems
Receptor, intracellular, second
Changes in cell function result from:
Receptor activation, intracellular signalling cascades, and second messenger systems
What are some examples of “activators” which change the conformation of target proteins?
Calcium and cAMP
Signalling molecules can regulate whether a G-protein has bound…
GDP or GTP
Phosphorylation is an example of ______________ modification
post-translational
G alpha s protein is associated with which enzyme?
Adenylate cyclase (activates)
G alpha i protein is associated with which enzyme?
Adenylate cyclase (inhibits)
Adenylate cyclase is associated with which second messenger system?
cAMP
G alpha q protein is associated with which enzyme?
Phospholipase C
PLC is associated with which second messenger systems?
IP3 and DAG
What is the effect of increasing/activating cAMP?
Results in an increase in phosphorylation
What is the effect of activating IP3/DAG?
Activating kinases
What is an example of a receptor activated by cAMP?
adrenaline receptors in lungs
What is an example of a receptor activated by IP3/DAG?
Muscarine ACh receptors
What is the enzyme that phosphorylates proteins?
Kinase
What is the enzyme that de-phosphorylates proteins?
Phosphatase
Serine/threonine kinases are _________ dependent
Calcium
What are cyclic nucleotides?
Second messengers, such as cAMP and cGMP
What ions can be transported through a ligand-gated ion channel?
Na+, K+, Ca2+, Cl-
Ions are transported along what type of gradient in a ligand-gated ion channel?
Electro-chemical
Ligand-gated ion channels open in response to changes in what?
The transmembrane potential
How are voltage-gated channels classified?
According to the ion that passes through them
Which type of receptor is comprised of a single, long polypeptide chain folded 7x with portions inside and outside of the cell?
GPCR
G protein coupled receptors are also known as
Metabotropic receptors
G alpha, G beta, and G gamma proteins are associated with which type of transmembrane receptor?
GPCR
What effect does the G alpha i protein have on phosphorylation?
Inhibits
What is the effect of stimulating the second messenger system cAMP?
activates proteins
IP3 and DAG activate __________
kinases
Acetylcholinesterase inhibitors are examples of drugs that work on what type of receptor?
Enzyme linked
Signals that are able to cross the cell membrane use what type of receptor?
Intra cellular (cytoplasmic/nuclear)
What are some examples of substances that use cytoplasmic or nuclear receptors?
Steroid hormones, thyroid, retinoic acid
Name some important second messengers in the nervous system (5)
cAMP, cGMP, DAG, IP3, and calcium ions
The difference in electrical potential energy per unit charge between two points.
Voltage (V)
In physiology, most voltages occur across a __________.
membrane
The flow of electric charge through a medium (through a surface)
Current (I)
The opposition to the passage of an electric current
Resistance (R)
The ability to conduct electric current; the measure of how easily electricity flows along a certain path
Conductance (the inverse of resistance)
How is Ohm’s law represented?
V = I (current) x R (resistance)
A property of cellular membranes that only allows certain molecules to enter or exit the cell.
Selective permeability
Differences in the concentration of ions in the opposite sides of a cell membrane lead to a
Voltage, or membrane potential (Vm)
This is a measurement of the overall electrical potential energy across the membrane
Membrane potential
The membrane potential (Vm) depends on the relative _______ current and ____________ of different ions.
electrical, conductance
Membrane voltage is described in terms of what happens to the ______________ face of the membrane.
Intracellular
When the inside of the cell membrane is POSITIVE (in relation to the extracellular facing part of the membrane), we say the membrane potential is
Positive
Cells have a resting membrane potential of
-70 to -90 mv
What creates current?
A flow of ions through a channel
The voltage across a membrane depends on which ions are currently…
permeable
Which ion is typically higher OUTSIDE of the cell?
Sodium (Na+)
What happens to the voltage of a cell membrane when Na+ channels open?
Passive influx of Na+ ions flow IN, making the voltage relatively more POSITIVE. (Think of depolarisation in an action potential)
What happens to the voltage of a cell membrane when K+ channels open (after action potential)?
Passive flow of K+ ions OUT of the cell, leading to the voltage becoming relatively NEGATIVE again (think of repolarisation).
Each ion has a “favourite voltage,” otherwise known as an
Equalibrium potential
What is the equilibrium potential for sodium ions?
+60 mv
What is the equilibrium potential for potassium ions?
-90 mv
What is the equilibrium potential for calcium ions?
+123 mv
What is the equilibrium potential for chloride ions?
-40 mv (or -65 in neurons)
If two ion channels were open and the cell was exactly equally permeable to both ions, the membrane potential (Vm) would go to the ___________ between the two equilibrium potentials.
average
Rapid changes in the Vm that spread rapidly along the nerve fibre membrane. It begins with change from normal resting negative Vm to a positive potential and ends with an almost equally rapid change back to negative potential.
Action potential
Movement of which ion is responsible for the depolarisation stage of the action potential?
Primarily sodium (though calcium channels also open)
The period of hyperpolarisation after K+ ions leave the cell is also known as the _________ period
refractory
What types of stimuli could cause a cell membrane to depolarise?
Electrical stimulus (such as a nearby cell depolarising) or a chemical stimulus (synaptic transmission where a NT opens a ligand-gated channel).
When Na+ moves into the cell, causing the membrane potential to move closer to 0, which leads to further depolarisation of the membrane, this is known as a
positive feedback loop.
At which voltage threshold is the cell committed to an action potential?
-65 mv to -50 mv
The majority of synapses are of what type- electrical or chemical?
Chemical
During an action potential, the increase in cytosolic free ________ triggers the release of chemical messengers (such as neurotransmitters).
calcium
Are chemical synapses unidirectional or bidirectional?
always unidirectional
In electrical synapses, the cells are in direct contact with each other and send ionic signals through a
gap junction
Action on a post-synaptic cell: input can either be ______ or ________.
excitatory or inhibitory
If sodium ion channels are open, this will lead to ____________ in the post-synaptic cell.
depolarisation
What are three ways that signals are terminated within the synaptic cleft?
- REMOVAL of neutransmitter from synaptic cleft
- DEGREDATION by enzymes
- RECYCLED into the pre-synaptic cells - (REUPTAKE)
