READING Flashcards
what is the difference between a neurotransmitter and a hormone?
- neurotransmitters are released in the brain
- hormones are released by the pituitary and travel in the bloodstream
- often structurally similar, the main difference between the two is the distance they have to travel
what is the difference between the electrical information flow in the nervous system and the flow of electricity in a wire?
- the electrical information flow in the nervous system is much much slower than the flow of information through a wire
- this is because in the nervous system it is the passage of charged ions that carry the current and not the passage of electrons
at resting potential, what side of the membrane has what charge?
the extracellular side of the membrane has a charge of -70mV relative to the intracellular charge of the membrane
the intracellular charge isnt actually 0 but we consider it 0 as when we look at potential differences we look at the extracellular charge relative to the intracellular charge
What is the difference between proteins made on the RER and proteins made from free floating ribosomes?
- proteins designed to be inserted into the cell membrane are made on the RER. This is because as the protein is being assembled it is threaded back and fourth through the membrane of the RER where it is trapped.
- neurons have a lot of RER because they have a lot of membrane proteins
- proteins destined to reside in the cytosol of the neuron is made in free floating ribosomes
what protein do microtubules consist of?
tubulin
what protein are microfilaments made of?
actin
what 3 structures make up the cytoskeleton in order of increasing size?
microfilaments
neurofilaments
microtubules
what distinguishes the axon from the soma?
there are no RER in the axon and very few free ribosomes
The protein composition of the membrane is very different in the axon
what is the name of axon branches?
axon collaterals
what are neurites?
axons and dendrites
How are dendritic spines correlated with intellectual disability
- intellectually disabled infacts have fewer dendritic spines and the ones they do have are abnormally long and thin
- the extent of the spine difference was well correlated with the degree of intellectual disability
what is the difference between unipolar, bipolar and multipolar cells?
unipolar- neuron has a single neurite
bipolar- two neurites
multipolar- multiple neurites
what is the difference between the pyramidal cells and the stellate cells in the cerebral cortex?
stellate cells are star shaped and are local circuit neurons
pyramidal cells are pyramid shaped and are projection neurons
what are the 3 main types of neurons in terms of what connections are made?
primary sensory neurons
interneurons
motor neurons
what is the difference between golgi type 1 neurons and golgi type 2 neurons?
golgi type 1
- otherwise known as projection neurons
- these have long axons that extend from one part of the brain to the other
golgi type 2
- otherwise known as local circuit neurons
- these have short axons that do not extend beyond the vicinity of the cell body
whats the function of ependymal cells
- they line fluid filled ventricles within the brain
- they play a role in directing cell migration during brain development
what is the equilibrium potential in relation to the membrane potential?
The equilibrium potential is the membrane potential that would balance out the ions concentration gradient so that no net ionic current would flow if the membrane were permeable to that ion
are k+ ca2+ and na+ more concentrated inside or outside the membrane
k+ is more concentrated inside the membrane
ca2+ and na+ are more concentrated outside the membrane?
which ways does the sodium pottasium pump transport ions across the membrane?
pumps na+ outside the membrane and k+ inside
uses atp as this is against the concentration gradients
which way does the calcium pump transport calcium?
outside the membrane
uses atp as against concentration gradient
what is the blood brain barrier?
a specialisation in the walls of the brain cappilleries that limits the movement of pottasium and other substances into the extracellular fluid of the brain
do electrical synapses exist
yes
where do electrical synapses occur?
gap junctions
gap junction often connect a neuron with a non neuronal cell, but they can connect two neurons in an electrical synapse
what are connexins and connexons
the proteins present in electrical synapses, they combine to form connexon channels. two connexon channels can then combine to form gap junction channels that allow ions to directly transfer from one cell to another
are electrical synapses directional or bidirectional?
they are bidirectional as gap junction channels allow ions either way
what is a neuromuscular junction?
a chemical synapse between motor neurons in the spinal chord and skeletal muscle
what is the post synaptic membrane of a neuromuscular junction called?
the motor end plate
what are the 3 major categories of neurotransmitters?
amino acids
amines
peptides
what is the difference between AMPA and NMDA receptors
AMPA are permeable Na+ and K+
NMDA are permeable to NA+ K+ AND Ca2+
NMDA-gated channels are voltage dependent
this is because at normal resting potential the NMDA channel is clogged by Mg2+ ions. Mg2+ is only unclogged when the membrane depoarizes. This usually follows the activation of AMPA channels at the same synapse
what two neurotranmitters mediate most inhibition in the CNS
GABA mediates most inhibtion
Glycine mediates most of the rest
what ion do GABA and Glycine channels allow in
Cl- ions
how do barbituates and benzodiazepines influence the GABAa receptors?
When GABA is present, benzodiazepines increase the frequency of channel openings and barbituates increase the duration of channel openings
- this results in more CNS inhibition
why does ethanol enhance inhibition in some brain areas and not others?
specific a,b and y subunits are nessercary for contructing an ethanol sensitive GABA
what 4 main protein subtypes do drugs bind to?
receptors
enzymes
carriers
ion channels
what is the difference between agonists and antagonists?
agonists activate the receptors and antagonists block the receptors
What is the difference between on target and off target side effects?
- on-target effects are unwanted side effects mediated through the same receptor as the clinically desired effects
- Off-target effects are unwanted side effects arising from the action of a different receptor
what is the difference between affinity and efficacy?
affinity is the tendency of a drug to bind to its receptors
efficacy is the tendency of it, once bound, to activate the receptors
what happens to the agonist log concentration-effect curve in the prescence of a competitive antagonist?
It shifts to the right, without a change of slope or maximum
what is a dose ratio?
the ratio by which the agonist concentration has to be increased in the presence of the antagonist in order to restore a different level of response
what is the relationship between the dose ratio and antagonist concentration?
there is a linear relationship between the dose ratio and the antagonist concentration
What are 3 features of reversible competitive antagonism?
- shift of the agonist log concentration–effect curve to the right, without change of slope or maximum (i.e. antagonism can be overcome by increasing the concentration of the agonist)
- linear relationship between agonist dose ratio and antagonist concentration
- evidence of competition from binding studies
what is irreversible competitive antagonism?
- Irreversible competitive (or non-equilibrium ) antagonism occurs when the antagonist binds to the same site on the receptor as the agonist but dissociates very slowly, or not at all, from the receptors, with the result that no change in the antagonist occupancy takes place when the agonist is applied
- with irreversible competitve antagonism the antagonist reduces the maximum response, however this may be hard to detect if there are a lot of spare receptors
whats stephensons formulation of efficacy?
- the reciprocal of the occupancy need to produce a 50% maximum response
- e.g e= 25 implies that 50% of the maximal response occurs at 4% occupancy
what is a full agonist?
a drug whose efficacy is sufficient that it produces a maximum response when less than 100% of receptors are occupied
what happens to the dose response curve of a full agonist in the presence of a partial agonist
- it shifts the dose curve to the right
- so in effect the partial agonist can act as a competitive antagonist to the full agonist
what is constitutive activation and what are inverse agonists
activation of a receptor when no ligand is present
sometimes a drug can reduce the amount of constituent activation and they are known as inverse agonists
why do agonists activate receptors and antagonists dont?
receptors have two states: Resting (R) and Active (R*)
Agonists have a higher affinity for R* so cause a shift of the equilibrium to R*
Antagonists have a neutral affinity for either R or R*
Inverse agonists have a higher affinity for R
What is biased agonism?
- some receptors can induce multiple different intracellular responses
- Biased agonists are more likely to induce one particular intracellular response from the same receptor
what is positive and negative affinity modulation?
positive modulation increases the affiity for the agonist, negative affinity modulation decreases it
what are 6 different mechanisms that give rise to tolerance and desensitisation?
- change in receptors
- translocation of receptors
- exhaustion of mediators
- increased metabolic degradation of the drug
- physiological adaptation
- active extrusion of drug from cells
How can change in receptors lead to tolerance or desensitisation?
receptors can change so that:
- agonists binding dont open the ion channel
- receptors are desensitised by phosphorylation
- phosphorylation causes the agonist to be less likely to induce a g-protein response
how does translocation of receptors lead to desensitisation
prolonged exposure to agonists can lead to a decrease in the number of receptors, due to receptors being taken into the cell via endocytosis
how does exuastion of mediators work
depletion of an essential substance
e.g amphetamines cause the release of amines from the nerve terminals however the amine store can become depleted
how does altered drug metabolism work
desensitisation can occur because increased metabolic degradation can lower the drug plasma concentration
