Membrane Flashcards
why is the MP -70 and not -90mv
- Membrane is most permeable to K+ at rest, but Na+ and Cl- ions are also
diffusing somewhat - K+ is the major player at rest = has the greatest permeability whereas Na+ and Cl- have low permeability
- mainly: Na+ has inward movement which counteracts K+ and makes membrane more positive
goldman equation
considers permeability og different ions
Em= (RT/F) ln (P[molecule 1]+p [molecule 2] on the outside/P[molecule 1] +p[molecule 2] inside)
If the membrane properties change to make the membrane most permeable to Na+
then there is a net Na+ current inward
* At equilibrium, there is a net cation accumulation inside the membrane
Na+ Equilibrium Potential
ENa+ is what
and how does it reach eqilibrium
+60mv, Na moves inside (influx inside) until + gathers and accumlates at the border at which point more posiitve Na is repelled back out
MP is -70 even tho Na is +60 because K+ is 90 so it has more influence
where is Cl- pushed and why
- Cl- ion is pushed out of the cell. more concentrated on the outside in the extracellualr space
- due to anion proteins present on the inside and not due to active pump. inside the cell we have large proteins (which are basically trapped, they can only get across to the outside using exocitosis), and they tend to have “-” charges.
Na+ Channel
- importance
- To generate a signal, membrane increases its what by
- In normal resting MP
- To open this Na+ channel we need to
- important to the intial phase of action potential
- To generate a signal, membrane increases its conductance by opening a channel permeable only to Na+ ion
- In normal resting MP, this Na+ channel is shut!
- depolarize (removing the polarization by making membrane more positive to move s4 segment up) the membrane by a certain amount
Na+ channel
- This Na+ channel is normally closed at
- This Na+ channel is only opened by depolarizing the membrane to a threshold potential of about
- more depolarization =
- -70
- -55
- more positive membrane, more Na more depolarization, cycle
Na channel inactivation and how to remove it
activation gate opens with rapid depolarization, and then 1/2 millisecond after, activation gate swings shut and prevents more Na from coming in. Without the gate swinging shut, MP will try to reach +60
2. To remove inactivation, the MP needs to fall below threshold again
- What’s an Action Potential (AP)?
- how to produce AP
- An AP is essentially an impulse, a very short lived, change in the MP, an AP is used as a signal
- You can only produce an AP in membrane that contains the voltage-gated Na+ channels. By definition, the presence of voltage-gated Na+ channel makes the membrane ‘excitable
Action Potnetial
- Na+ channels occur in
- When channels are open
- But channels rapidly inactivate and Na+ inactivation leaves
- Na+ channels occur in high density within ‘excitable’ membranes
- When channels are open, membrane potential surges towards ENa+ = 60 mV
- Na+ inactivation leaves K+ leakage as main current, and resting potential is
restored
Battle between Na and Ka. When Na is open, it is dominant but it doesnt open for too long so Ka is mostly dominant
what is threshold
three types of threshold
all or none principle
- Minimum depolarization necessary to induce the regenerative mechanism for the opening of Na+ channels
- subthreshold, theshold, suprathreshold
- Action potential from threshold and supra-threshold stimulus have the same magnitude. You either have AP or not.
Frequency coding
Information pertaining to stimulus intensity is coded by the changes in the
frequency of the Action Potential. Frequency codes for intensity
Refractory Period
- After we generate an AP and inactivate the Na+ channels, we have a period in which
- Na+ channels remain inactivated until
- Absolute RP
- Relative RP
- we have a period in which all or some Na+ channels are inactivated
- Na+ channels remain inactivated until membrane potential drops below
‘threshold’, then channels reconfigure to their original state and membrane becomes excitable again - Absolute RP: none of channels are reconfigured. All Na are inactivate which restires resting state
- Relative RP: some but not all of channels are reconfigured (generally 2-5 ms duration) Na channels slowly, at diff speeds reconfigure and become activated. This could generate an action potential
how to completely block membrane from producing AP
Keep the membrane depolarized! u permanently depolarize the membrane, keep it at 20 mV (above threshold), the Na+ channels will be permanently inactivated, and you will not be able to generate another AP
Depolarization Block
How can we keep the membrane depolarized?
destroy the concentration gradient for K+ (remember that K+ current is responsible for keeping the MP polarized to -70 mV) by introducing more K+ in the extracellualr space (excess [K+]o — e.g. with KCl
injection) * This will result in permanent Na+ inactivation and the membrane will remain in absolute refractory state and the membrane becomes in-excitable
After-Hyperpolarization
- K+ channels are needed to repolarize the membrane
- Due to the presence of this “extra” K+ channels, in conjunction with the leakage K+ channels, we have much greater outward K+ current
- This results in the MP to be more polarized than normal
- Thus, the voltage-gated K+ channels cause a hyperpolarization after the AP
- So instead of the MP being
repolarized to -70 mV, the
MP might be repolarized to
-80 mV
Impulse Conduction
- what happens when a patch of excitable membrane generates an action potential
- The local reversal in potential temporarily goes from x on the inside to y on the inside.
- This local reversal in potential serves as the
- Na channels opened and once started AP will
- When a patch of excitable membrane generates an action potential, this causes an influx of Na+ and reverses the potential difference across the membrane.
- The local reversal in potential temporarily goes from “-” on the inside to “+” on the inside.(from -70 to +30
- This local reversal in potential serves as the source of depolarizing current for adjacent membrane which depolarizes the next membrane, so on and so forth
- AP will propagate from its origin across the rest of the cell until it reaches axon terminal
Excitable Cells
- why are most cells not excitable (generate AP)
- what will they do instead
- why are most cells are not interested in carrying a signal any distance
- what is an axon
- what neurons can generate propagating action potentials
- that they lack voltage- gated Na+ channels
- These cells will however conduct passive currents, but will not generate APs
- they don not have an ‘axon’
- An axon is a long extension of the cell body (like a wire) that carry AP away to some other location
- only neurons with long ‘axons’ and muscle cells generate propagating action potentials
- what happens in biological tissue if we put a votlage across membrane on one location
- why
- In biological tissue if we put a voltage across membrane on one location (i.e. step change in voltage) and measure the voltage across the membrane some distance away > It doesn’t look anything like what we started with. It will decrease
- Membrane property shape the form of the signal . We are losing signal as the current travel along the membrane
length constant
what does it measure what depends on it
measures how quickly a potential difference disappears (decays to zero) as a function of distance. defined as the distance you can travel, to the point where the voltage drops to about 37% of its original value
* Ideally, you want to increase as much as possible so that the depolarizing current will spread a great distance
* Thus, the conduction velocity of an AP along an axon depends on the membrane length constant,
What are the mechanisms involved in the system to improve lambda ?
- (lambda) is increased by increasing diameter (The larger the diameter > less internal resistance > less voltage is lost across that resistance as the currents travel down the membrane)–
- Lambda is increased by increasing membrane resistance (The higher the membrane resistance > less current is leaked out > current is forced down the membrane)
lambda defined as x to the point where the voltage drops to about y% of its original value
what do you want to do ideally and why
lambda is defined as the distance you can travel, to the point where the voltage drops to about 37% of its original value
Ideally, you want to increase as much as possible so that the depolarizing
current will spread a great distance
- what is the most effecient means of
increasing conduction velocity - what are glial cells
- what are Specialized ‘glial’ cells
Increasing membrane resistance (i.e. myelination) is the most efficient means of increasing conduction velocity
* ‘Glial’ cells are cells that serve as a myelin sheet on the outside of the axon and assist the nervous system, they are required for nutrition and increased membrane resistance. Act as a glue to the system
* Specialized ‘glial’ cells (Schwann cells of the PNS or oligodendrocytes within the CNS) wrap around successive sections of an axon > myelin sheath. Schwann and Oligo= myelin sheath
Meylination
how many layers and what does it do
50-100 layers wrapping around the
axon > this greatly increases the
membrane resistance > reduces the
leakage of current out of the
membrane
shwann cells wrap around what
Oligodendrocyte has a number of
processes that do what
Schwann cell wraps around a single
portion of the one axon (cytoplasm is
all squeezed-out)
Oligodendrocyte has a number of
processes that streaks out like an
octopus and wraps a whole bunch of
axons individually
rode of ranvier
There are small gaps left between adjacent portions of the myelin sheath (a glial cell will wrap one section and next glial cell will wrap
another section)
* This small gap left between adjacent glial cells > the ‘Node of Ranvier’
Saltatory Conduction
In myelinated axons, only what is excitable and what does it means
- In myelinated axons, only the membrane exposed at the nodes is excitable
- Because the APs are only generated at these nodes, it means that the AP will ‘jump’ from one place to the next and in between, you’re not generating any AP
- This ‘jumping’ mode of conduction is known as ‘saltatory conduction’
Saltatory Conduction
how does it work, suffenciency, and what prevents leakage
Thus, if we have an AP on one node, the depolarizing current that is generated at the site is strong enough and will travel down that axon for many nodes (5-10 nodes)
* There is sufficient strength to bring all the following nodes to threshold potential
* Therefore, AP at one node will bring all the next 5-10 nodes to -55 mV to generate APs on all the next nodes simultaneously and passive spread of depolarizing current occurs between the nodes (myelinated portion) to generate AP
* myelin prevents leakage of current across membrane between nodes
safety factor of Saltatory Conduction
You could poison some of the nodes and the depolarizing current will just skip past that and move on to the next healthy patch of membrane (i.e. you have to destroy a fair length of the membrane to stop AP in its track)
things about Unmyelinated Axons
4 things
- The unmyelinated axons do not have this extensive wrapping around the outside > you get lots of current leakage and slows down the conductance velocity
- Slow conduction velocity (small axon diameter and low membrane resistance)
- Both Na+ and K+ voltage-gated channels are intermixed
- Majority of axons are unmyelinated
*
remark bundle
Unmyelinated axons do have some insulation: the schwann cell and
oligodendrocyte engulf the axon (5-30 axons) without winding > “Remak Bundle” which imposes some membrane resilence
Axon terminal
AP will be conducted along to what
at the end of the cell, AP is still
So why not just go backwards to
where it came from?
- AP will be conducted along the
membrane right to the end of the
cell > at the end of the cell, AP is still
generating depolarizing currents - AP cannot turn around and repropagate in direction it came from
because of refractory period (the node before goes through refractory), the
volt-gated Na+ channels are
inactivated - So at the end of the axon, the AP
dies-out…it can only go one way
Electrical Synapse
distance
what does it do
- 2 neurons linked by gap junctions
At electrotonic synapses (gap junctions),
adjacent membranes are about 35Å
apart - Gap junction bridged by connexins which allow small ions (and depolarization) to cross
bidirectional
chemical synpase
what is released and where
synpase is defined by
how wide
why is specialized
- The transmitter is released into the extracellular space which exists between adjacent cells
- The synapse is defined by the presynaptic surface (the bouton, which contains the vesicles) and the postsynaptic membrane, which is the membrane of the adjacent neuron
- Synaptic cleft (the space) is about 200 Å wide
- This space is very specialized due to the existence of postsynaptic membrane, which contain specific protein receptors which will bind that transmitter molecule after it’s released
- Chemical synapses are processing stations
Axon terminal
Axons end in
what are vesicles
probability of vesicle release
Axons end in ‘boutons’ filled with vesicles
* vesicle are tiny organelles, which contain neurotransmitters which is released into the extracellular fluid through exocytosis
* Note that vesicle release is probabilistic – 1 AP has a 10-90% chance of releasing 1 vesicle
Vesicle release
- trigger for exocytosis
- how do we get Ca+ ions in
- what happens normally in preperation for fusion
- Ca+ ions
- Bouton membrane contains voltage-gated Ca++ channels which open when depolarized by AP currents
* AP depolarizes the bouton membrane > reaches threshold for opening volt-gated Ca++ channels (-50mV)
* Ca++ diffuses into bouton, and triggers cascade of reactions which result in vesicle exocytosis (commonly ‘kiss & run’ type = transient OR full fusion = all transmitters are released) - Normally, vesicles are docked in preparation for fusion, we have a set of vesicles which are lined-up and ready to go
Post synaptic Receptors
Transmitter agent does what and binds where and what does this binding do
Receptors are either
what determines effect
- Transmitter agent diffuses across synapse and binds to a specific site on a
receptor protein embedded in postsynaptic membrane - Binding of transmitter causes a change in shape of the receptor protein
- Receptors are either – Ionotropic (directly opens channels) – Metabotropic (initiates a metabolistic cascade to activate enzymes)
- Receptor determines the effect, not the transmitter
Ionotropic Effects
- Ligand binding opens an ion channel > Ionotropic
- immediate effect
- Binding of the transmitter to the post-synaptic membrane results in change in the post-synaptic membrane potential, this is called the Post-Synaptic Potential (PSP)
- The duration of PSP is about 20-40 ms (as long as the transmitters are present)
- Ion channel may be specific for cations (Na+, K+) > EPSP (excitatory) (depolarizing= making MP more +)
- Or ion channel may be specific for Cl- or K+ ion > IPSP inhibitory (hyperpolarizing makes MP more -)
ex: Nicotinic receptor for Acetylcholine
Ligands for Ionotropic Receptors
4
Acetylcholine (Ach)
– Glutamate
– GABA
– Glycine
It’s the receptor that determines the effect and not the transmitter
Metabotropic Effects
- Binding of the ligand to the post-synaptic metabotropic receptor activates an enzyme that is usually G-protein coupled
- The enzyme facilitation will result in increase (production) or destruction of 2nd messengers
- activation takes time because it goes through enzymatic activity
**2nd messengers, **
what are they, what do they do, what happens when you phosphorylate membrane proteins
- 2nd messengers are either cAMP, cGMP, or InP3
- 2nd messenger then activates other enzymes, e.g. phosphokinases which
phosphorylate membrane proteins or other proteins in the cytoplasm - If you phosphorylate membrane proteins (i.e. ion channels) > result in modulation of ion currents
beta-Adrenoreceptor
What is it
binding activates x via y
x increase what which then activates what to phosphorylate what and what does this phosphorylation do
- b -receptor is a metabolic receptor for Noradrenalin (NA)
- Binding of NA to -receptor activates adenylyl cyclase via G-protein alteration
- adenylyl cyclase increases production of cAMP (2nd messenger)
- cAMP then activates kinases which phosphorylate membrane Ca++ channel
- This phosphorylation of the Ca++ channel > increase in Ca++ influx (important in heart muscle, increases contractility)
ex: b-blockers: decreases Ca
Ligands for Metabotropic Receptors
6
- ACh: Muscarinic receptor
- Peptides: substance P, b-endorphin, ADH
- Catecholamines: noradrenaline, dopamine
- Serotonin
- Purines: adenosine, ATP
- Gases: NO, CO
Spread of post synaptic potentials
1.where are they generated
2. where is the nearest excitable membrane
3. what generates psp
4. how does it spread
- PSPs are generated in inexcitable
membrane: neuronal dendrites and
cell bodies (these areas do not have
high density of voltage-gated Na+
channels) - Thus, they can NOT initiate an AP
- Nearest excitable membrane is at the
beginning of the axon > trigger zone - Binding of transmitter > generates PSP
- PSPs must spread through passive conduction across the membrane to get to the initial segment of the axon
PSP Summations
why do we need them
2 types
- Biological tissues have poor cable property (compared to telephone cables) Thus, there will be loss of current (potential) as you go along the membrane before reaching the trigger zone
- Spatial summation: and temporal summation
Spatial Summation
3 steps
- minimum of 10-30 synchronous EPSPs in dendritic tree, each generated at a different synapse
- Large number of EPSPs in synchrony (silmutaneous)
- must overlap in time
- x # exitatory neurons fire. Their graded potentials spereatly are below threshold
- graded potentials arrive at trigger zone together and sum to create suprathreshold signal
- action potential is generated
Temporal Summation
- only a few active synapses, but each generating EPSPs at high frequency; summated potentials reach threshold over a period of time
- ## EPSPs last for about 30-40 ms in duration before dying out, thus, successive inputs on any given synapse generates subsequent EPSPs that add on to pre-existing EPSPs (e.g. 10 ms apart)
Inhibitory Post-Synaptic Potential
- location
- strategic advantage
- IPSPs tend to be preferentially located on the cell soma (cell body), interposed ½ way between the site where EPSP is generated and the trigger zone
- IPSPs have strategic advantage: due to its location close to the trigger zone > can shunt depolarizing EPSP currents out of cell
IPSP and Cl- Channel
- what do IPSP do do the cl channel
- Cl- eq potential
- opening cl- channel when membrane is depolarized vs at rest
- net effect of cl-
5.
- IPSP involves the opening of the Cl- channel
- IPSPs in general in the Nervous System,
are more important than EPSPs - The equilibrium potential for Cl- is very close to the resting MP (-70 mV)
- Therefore at rest, opening of the Cl- channel would result in little change
- However, when the membrane is depolarized, opening of the Cl- channel will bring the MP back down to -70 mV
- The net affect of Cl- is basically to ‘clamp’ the MP, which is preventing excitation, thus preventing depolarization > inhibitory effect
- These IPSPs are very strategically located and they completely block any signal coming from EPSPs simply by positioning right on the soma
initally more Cl- exists outside the cell because it is recycled by proteins
Spike Train
- what happens when when summated EPSPs arrive at the trigger zone?
- But what happens when you have a very powerful synaptic input to the postsynaptic neuron persisting in time lasting up to 500 ms?
- How to generate a spike train
- It’s easy to see that when summated EPSPs arrive at the trigger zone, it achieve threshold and an AP (spike) is triggered
- Depolarizing the trigger zone to threshold and sustain that depolarization for 500 ms, you want that powerful input to be translated into continuous stream of APs > This is called the ‘Spike Train’
- If we depolarize the membrane above threshold and keep it there, you’ll get one AP and the voltage-gated Na+ channels will inactivate (refractory period) and you can not get another AP until the membrane repolarizes
* Therefore, after each ‘spike’ we need to get the membrane ‘hyperpolarized’ to restore the Na+ channels to re-open them for the next one
* We must have Hyperpolarization to generate another AP, otherwise we’ll never generate a ‘Spike Train’
* The idea is to overcome the depolarization block
After-Hyperpolarization
- what triggers After-Hyperpolarization
- Hyperpolarization after each spike ensures that
- what happens After the hyperpolarization fades away
- what is generated because of afterhyperpolarization
- Voltage-gated K+ channels at trigger zone cause afterhyperpolarizations
- Hyperpolarization after each spike ensures that Na+ channels reconfigure, and membrane excitability is restored
- After the hyperpolarization fades away (voltage-gated K+ channels will close when the membrane is repolarized), the MP will be able to shoot right back up where EPSP is taking it and cross the threshold again and a whole new spike and this will repeat until the EPSP fades away
- Thanks to afterhyperpolarization we could generate a ‘Spike Train’
Receptor Potential
what is it
how does it react and what does it cause
Receptor potential: change in the MP due to receipt of signal from exterior
sensory cue
* The energy from the environment will react with membrane proteins and in general this will cause depolarization of sensory receptors upon receipt of specific energy
Receptor Potential
where is it
how do they work and this results in two things
- Similar to PSP, the receptor proteins are embedded in sensory cell membrane
- The receptor proteins of the sensory cells will change shape when specific energy is received
- When the receptor protein changes shape, it can either:
– Directly open ion channels (e.g. cation channels > leads to depolarization of themembrane) (like ionotropic)
– Enzyme is activated via G-protein coupling > leading to production of 2nd messenger (cAMP, cGMP, InP3) > lots of 2nd messenger > amplifying the signal (like metatropic)
receptor potential
binding of metabotropic receptor and how it works
6 steps
Chemical stimulus binds to specific metabotropic receptor (G-protein coupled) > activation of G-protein > activate adjacent enzyme (adenyl cyclase) > produces 2nd messengers (cAMP) > cAMP activate kinases > directly interact with ion channels or phsophorylate other proteins
2 stages of amplification
– G-protein can activate a number of different enzyme molecules
– Each of these enzyme molecules will produce lots of 2nd mesenger (cAMP)
* Thus, one stimulus molecule can produce lots of 2nd messenger (cAMP)
Olfactory Receptor
how does it work 6 steps
Specific receptor proteins bind specific odorant > activate G-protein > activate adynyl cyclase > production of cAMP > cAMP directly binds to ion channels > allow cations (Na+ and Ca++) to go through > depolarization of the membrane which **could ** lead to AP
- The depolarizing current has to travel down the membrane and down to the trigger zone of the axon
Categories of sensory cell transmission
– Sensory cell generates an action potential at a spike-generating zone
– Sensory cell releases vesicles when depolarized; impulses generated in post-synaptic neuron
Transmission of AP Signal
how to open ion channels
Sensory cell generates an action potential at a spike-generating zone
- Located at the axon terminal (e.g. in the sensory axon innervating the skin). First patch of excitable membrane will generally be at the branch point; thus, the receptor potential will have to travel and generate summation at a branch point to reach threshold to get an AP
- Pinch and apply pressure to open ion channels
transmission of signal vesicles
- release of neurotransmitter
- The depolarizing current don’t produce any AP > travel throughout the
membrane and at the other end > they depolarize the membrane sufficiently > influx of Ca++ ions and trigger exocitosis vesicles > sensory cell is releasing
vesicles and not producing an AP
taste receptor
RP travel throughout the membrane
and at the other end > influx of Ca++
ions > vesicles released vesicles (not
producing an AP)
Adaptation (2 things and 2 types)
- The MP can decay over time leading to ‘Adaptation’
- The original voltage is not sustained and it’s dropped over time, even though the stimulus may be constant
- Types of adaptations
– Slowly Adapting: receptor potential sustained for duration of stimulus. Interested in overall magnitude of the stimulus
– Rapidly Adapting:receptor potential elicited by change in stimulus energy, decays to zero when stimulus is constant - Interested in how quickly the stimulus is being delivered, the velocity of stimulus being delivered
Habituation
Habituation is the response to successive stimuli in time
* Habituation: repeated stimuli (identical) in succession elicit progressively weaker responses
* Habituation response depends on the cell, some will show large degree and some won’t
**
Coding of Stimulus Intensity **
1. how does Receptor potential vary?
2. greater stimulus = and greater depolarization=
3. what limits impulse frequency
- The receptor potential they will vary directly in proportion with the intensity of the stimulus
- Greater the stimulus intensity > greater the receptor depolarization (bigger change in mP) (graded potential) > more transmitter released and/or higher AP frequency
- The greater the depolarization > the faster the membrane will be brought up from hyperpolarization to generate a new spike
- The Impulse frequency will always be limited by the refractory period
Coding of Stimulus Intensity
After a while, you will reach a ceiling due to refractory period. What if you want to do coding above this ceiling
- The strategy is to recruit additional neurons
- As stimulus intensity increases, we recruit higher threshold sensory neurons: we need a very intense stimulus before higher threshold sensory neurons are released
strategies to code for the strength of stimulus
– Increase frequency of AP at excitable membrane (increase intensity of stimulus > increase frequency of AP [receptor A])
– With increasing stimulus strength, we recruit an additional receptor B, which has a higher threshold
Coding for Modality
- How are we going to distinguish different modality (quality) of stimulus? and what does it mean
- Within a modality, we could have a variety of stimulus qualities. All sensations have sub-modalities that you could distinguish. If you had to devise receptor proteins for ALL these qualities, it won’t be efficient. Is there a better way?
- We use a ‘Labeled Line’ strategy
* This means that activity in one pathway means a particular stimulus quality and nothing else - Population coding is coding using the ratio of activity from a restricted number of different receptor types
* Specific stimulus is coded by ratio of activity across the population of receptors
* * A given receptor (e.g. A), type will respond to a wide range, but it has a peak and that is different from others
* Thus, any given stimulus (dotted line) will activate one receptor (C) very strongly but others (A, B) more weakly
receptive field
3 things
- Each sensory neuron is going to respond to a particular spatial area (e.g. skin, it’s the territory on the skin) > Receptive Field
- Receptive Field of a given sensory neuron is the territory in which you could activate that neuron
- Receptive Field is always defined in relation to a given sensory neuron, each sensory neuron will have a different Receptive Field
- Receptive Field in cutaneous sensory neuron is the skin territory in which
adequate stimulation elicits a response and is generally about 10-20 mm across (in the fingertips, it can be as little as 1 mm across)
Blood-Brain Barrier
- what are protected from the general circulation and the body
- how is The ionic composition of the extracellular fluid around the neuron
carefully controlled: - Thus, the extracellular fluid in the neuronal environment (
- The brain and the spinal cord are protected from the general circulation and the body
- The ionic composition of the extracellular fluid around the neuron must be
carefully controlled:
– Can not change the excitability of the membrane (e.g. with KCl injection > decreased K+ concentration gradient > depolarization > inactivation of the Na+ channel > no more AP produced)
– Can not have neurotransmitters floating around for no reason - Thus, the extracellular fluid in the neuronal environment (brain and spinal cord) are carefully regulated through Blood-Brain Barrier (BBB)
seperation of blood brain barrier (pie chart)
Between Blood Vessels & Interstitial Fluid and Blood Vessels & CSF
Free diffusion between CSF and interstital fluid (similar chemical composition)
Areas lacking the BBB
- Most of the brain is protected by BBB, but
- At some places it is essential for neurons to
- The pituitary gland (releases hormones) is directly connected to the..thus
- what happens in ‘Circumventricular organs’
- Generally, BBB is broken in areas that
- Most of the brain is protected by BBB, but it is not continuous
- At some places it is essential for neurons to communicate freely with the blood stream (e.g. hypothalamus)
- The pituitary gland (releases hormones) is directly connected to the
hypothalamus > thus, BBB is purposely broken to allow release of hormones - In ‘Circumventricular organs’ (around 3rd ventricle) the BBB is broken so neurons can sense specific chemical [ ] 5. Generally, BBB is broken in areas that interact with endocrine system or require sensitivity to metabolites in plasma
Brain Encasings
3 including the various meninges
- Skull/ Backbone (1st line of defense)
- Meninges:
– Dura mater (very tough membrane,
sac containing the brain and the
spinal cord)
– Arachnoid membrane (much more
delicate tissue)
– Pia mater (lies right on top of the brain; tethered to Arachnoid by
Arachnoid ‘Trabeculae’)
– Between the arachnoid membrane
and Pia matter > Subarachnoid space
(filled with CSF) > brain floats to
protect from mechanical stress - Reticular formation: collection of loose nerve cells responsible for behaviour. Located between brain and spinal cord
what do we have in the subarachnoid space
In the subarachnoid space, we have
blood vessels > capillaries to the
brain tissue > BBB, in between the
capillaries and the brain tissue
- The endothelial lining of the BV, mostly contain x through which y
- In Brain, endothelial cells are x > this constitutes
- The endothelial lining of the BV, mostly contain large gaps (fenestrations), through which molecules can pass
- In Brain, endothelial cells are tightly bound leaving no gaps > this constitutes the BBB (everything has to be transported)
- what are vetricles
- name the ventricles and how they are connected
- The ventricles are cavities deep inside the brain filled with cerebral spinal fluid
- A large curving Lateral Ventricle (LV) inside each cerebral hemisphere, a paired structure across the midline
- The LV empties into the 3rd Ventricle, right in the middle, deep in the brain under the cerebral hemisphere
- The 3rd Ventricle communicates via a channel called “Aqueduct of Sylvius” to the 4th Ventricle
- From the 4th Ventricle, we have a canal, “Central Canal” which goes in the middle of the spinal cord
ventricles
- CSF produced in the ventricle drains through
- CSF then moves to and finally exists at x into y
- this all CSF eventually draisn into either
- About x CSF drains through
x into the y
- CSF produced in the ventricle drains
through the ventricle of the central
canal - CSF then moves to outer parts of the
brain (subarachnoid space) and
finally exits at the top of the brain
into large venous sinus (on the
midline) back to general circulation - Thus all the CSF eventually drains
into either venous sinus or veins
somewhere along the line - About ½ CSF drains through
‘Arachnoid villi’ into the venous
system
Circulation occurs without a pump
Arachnoid Villi
- Arachnoid Villi is an out pouching of
the arachnoid tissue, sticks out
through the dura matter into the
venous sinus > CSF drains into the
venous system
- Ventricles are filled with CSF, which is
- CSF is produced from x by y which
- Ventricles are filled with CSF, which is the bathing medium of brain (highly
regulated ionic content, few macromolecules) - CSF is produced from plasma by ‘choroid plexus’, which lines the ventricles (LV, 3rd, 4th, all have choroid plexus producing CSF)
Choroid Plexus
what is it, what is it made up of, what does it do, structure
- Choroid Plexus produces most of CSF (but not all, some are produced in the capillaries inside the brain)
- Made up of epithelial cells connected by tight junctions
- Choroid Plexus produces CSF continuously (550 ml/day) to circulate cleansing mechanism
- Choroid Plexus is a dense network of capillaries ballooning out into the ventricular wall with tight junction so that everything has to be transported
Cerebrospinal Fluid
- CSF is produced by x in y
- CSF fills what 2 things
- CSF has same (2 things) as blood
- Greatly reduced 3 things
- Total volume on an average person is
- Cranial CSF is x mL and the spinal CSF is y ml
- Thus, most of the CSF is in the x serving as ‘cushion’
- CSF is produced by ‘Choroid Plexus’ in ventricles
- CSF fills the ventricles and the subarachnoid space
- CSF has same osmolarity and [Na+] as blood * Greatly reduced [K+], [Ca2+] and [Mg2+]
- Total volume on an average person is 215ml
- Cranial CSF is 140ml (25ml in ventricles, 115ml in subarachnoid space) and the spinal CSF is 75ml
- Thus, most of the CSF is in the subarachnoid space, serving as ‘cushion’
we make 500ml of CSF a day: replace CSF 3x a day
a diagnostic, therapeutic procedure >
collect sample of cerebrospinal
fluid (CSF) for analysis
A lumbar puncture (spinal tap)
Astrocytes
4 things
- The walls of the capillaries are plastered with the ‘end feet’ of glial cells,
particularly the astrocytes - Astrocytes provide a bridge between neurons and blood vessels.
- Astrocytes are efficient at glycolysis
- Astrocytes produce lactate as an end-product
- Lactate is a substrate for ATP production
2 functions of astrocytes
– Remove neurotransmitters because they sit right on the synpase
– Provide energy substrates for neurons and more
* They are following and latching on to BV (some end feet latched onto the BV and the others with neurons)
Astrocytes also regulate local blood flow, but how?
4 steps
- Astrocytes are already bridging the gap between BV and neurons, so they are in good spot to signal BV when to dilate and to constrict (increase or decrease blood flow)
- Astrocytes have connection with the neuron at the synapse and when they detect increased signaling, they can send a metabolic signal outward to BV (opposite to nutrient flow), signaling neuronal activity level
- Glutamate in synapses triggers Ca2+ release within astrocytes; Ca2+ wave travels through astrocytes and triggers prostaglandin (PGE2) release at end-foot
- PGE2 causes vasodilation > increased blood flow
