BMS11004 - WEEK 4 TUESDAY, WEDNESDAY, THURSDAY Flashcards
brain extracellular fluid, BBB, ventricular system, CSF, neurons, astrocytes, blood vessels
what is the neuronal microenvironment made up of
glia, capillaries, other neurons, extra-cellular space
what is extracellular space made up of
extracellular matrix (structural support), BECF (brain extracellular fluid)
how can BECF influence, and be influenced by neuron
increased neuronal activity impact changes in BECF composition and continue round in loop
why must BECF composition need to be tightly regulated
neuronal dysfunction or death
how can neuronal activity change BECF composition
increased K+ conc on outside of cell
changes in Ca2+ conc
changes in O2, glucose, CO2 conc
increased H+ = acidification
NT conc
how could a change in BECF composition change neuronal activity
increased K+ conc in BECF increases resting potential bringing cell closer to threshold for firing AP
increased NT release, leading to unspecific receptor activation = unspecific neuronal activity
name 4 ways of regulating neuronal microenvironment, and BECF
- BBB
- CSF in ventricular system
- neurons
- glial cells
how can you study BBB in research
intravenous dyes injection, pass through leaky capillary and stain soft tissues but no stains in brain
what is function of BBB
protect neuron from blood-substance conc fluctuation
-increased amino acid conc post-food
-increased K+ H+ conc after exercise
-circulating hormones
-inflammatory mediators
-toxins
how is BBB maintained, and how can important molecules pass by
tight junctions between endothelial cells, astrocytic endfeet, thick basement membrane
passes via facilitated transport, exchangers, co-transporters, many mitochondria in endothelial cell (more ATP), diffusion of small uncharged lipid soluble molecules
what are transport exchangers
proteins moving ions in opposite direction
what are co-transporters
proteins moving ions together
where are leaky regions of BBB
choroid plexus (ventricular system = where CSF made), circumventricular organ
what do leaky regions of BBB allow
hormone release, osmoreceptors (OVLT, subfornical organ, hypothalamus) detect osmolarity of blood and cytokines, activating temp control centre so brain can directly analyse blood for infections
explain layout of cavities and ventricles in ventricular system in brain
4 cavities
2 lateral ventricles in cerebral hemispheres, come down meet 3rd ventricle and cerebral aqueduct into 4th ventricle to brain stem (medulla, pons, cerebellum)
what does CSF do
physical buffer for protection
maintains ion levels between intra/extracellular fluid and BECF
remove waste product
what is in CSF
similar to blood (no RBC, platelets)
less K+, amion acids, protein
what is exchanged form CSF to BECF
macronutrients eg; glucose
micronutrients eg; vitamins
ions eg; HCO3-
what is exchanged from BECF to CSF
metabolic waste products eg; CO2
NTs which are not recyled
outline flow of CSF
secreted by choroid plexus, circulate around ventricles, down to central canal and foramen
absorbed from subarachnoid space to venous blood system at superior sagittal sinus
how much CSF produced per day
500 mls
how it extracellular fluid prevented from accessing CSF
tight junctions and selective absorption of substances into CSF across choroidal epithelial cells (AT/facilitated diffusion)
name 3 type of meninges
pia mater
arachnoid mater
dura mater
give properties of pia mater (inner)
soft, pliable, thin membrane, quite permeable
give properties of arachnoid mater (middle)
under subarachnoid space, has tight junctions
give properties of dura mater (outer)
thicker, important for structure
where is CSF forced out of arachnoid granulations into
superior sagittal sinus
outline details of arachnoid membrane envaginations
arachnoid granulations (up to 1cm)
arachnoid villi (smaller)
many tight junctions to prevent things moving in between cell
outline bulk movement of CSF out of subarachnoid space
via vesicle across membrane into venous sinus
how does more CSF move across into venous sinus
increased absorption with increased intracranial pressure
more CSF made, more pressure is generated in subarachnoid space, so more CSF moved across into venous sinus
how is hydrocephalus created
too much CSF production (not enough absorption)
dilation of ventricular system
obstruction in ventricular system/interrupted CSF absorptions
increased intracranial pressure
loss of brain cell, loss of brainstem relfex
where do neurons and astrocytes terminate neurotransmission
tripartite synapse
what ions does neurons and astrocytes remove from extracellular space, and how
K+, via pump into cell to keep intracellular K+ greater than in extracellular, to maintain equilibrium
what does increased K+ cause astrocyte to start
increase glucose metab to help neuron
shuttle lactate to neurons and allow pumps to keep pumping more K+ into cell (using ATP conversion)
increased K+ uptake
what is equilibrium potential for K+ in both neurons and astrocytes
-90mV
what is neurons resting MP
-65mV
what is astrocytes resting MP
-85mV
do astrocytes or neurons have higher K+ selectivity
astrocytes
also has more selective membranes to K+, more extracellular K+ will influence Vm
are astrocytic or neuronal membranes more permeable to Na+
neuron
how to astrocytes communicate (chemical synapse or gap junction), and what does this create
use gap junctions which creates syncytium = intracellular compartments connected via gap junctions without having to release into any extracellular spaces
what do connexins do in astrocyte
create pore from one astrocytic intracellylar compartment to another astrocytic intracellular compartment
if neurons create lots of K+, nearby astrocyte can uptake and pass onto others without it making contact with extracellular space, redistributing K+ to areas of decreased activity
can also transport sugars, aa, cAMP, Ca2+ through gap junction via syncytium
what is neurovascular coupling
couple neuron activity to vascular activity
how can astrocytes detect if neuron is very active
from dendritic spine (release lots of NT, AP) and attach themselves to arterioles to release things modulating muscles activity surround blood vessel, to relax/contract, to increase/reduce amount of O2 entry
how does MRI work
3D, structural, H+ atoms align in scanner, radio wave cause H+ facing new direction. when relax and return to old position, emit resonance
how strong is MRI
0.5-3T, 60T in research
what do radio frequency coil in MRI do
radio frequency coil directs wave, detect bounce back wave
what do gradient coils in MRI do
other magnets, lower strength, adjusts field
how does PET work
label glucose, injects radioactive tracer, absorbing into bloodstream and measure volume in brain to show active area
Neuron A has an axon twice as wide as neuron B’s axon. If everything else is same between 2 neurons, how long is neuron A’s space constant compared to neuron B’s space constant?
A’s space constant is sqrt (2)times (ie. 1.4 times) longer than B’s space constant
What’s wrong with this statement? “If myelin makes AP go faster by insulating axon, AP would go even faster if entire axon is insulated, even Nodes of Ranvier”
Nodes of Ranvier are necessary for voltage-gated Na+ channels, to allow the propagation of signal (signal needs generation by sodium channel)
What would happen to neuronal conduction speed if you insert a lot of K+ leak channels into membrane (ie. K+ channels that are open at resting potential)
decrease: membrane resistance goes down, shorter space constant
Given [Ca2+]I = 0.0001mM, [Ca2+]o = 1mM, what is Nernst potential of [Ca2+]
- ECa2+ = 61.54mV log Ca2+ outside/Ca2+ insideECa2+ = (61.54/2) log (1/0.0001)ECa2+ = +123.08 mV
Why does botulinum toxin cause paralysis?
- targets and destroys SNARE proteins, (these are ‘zippers’ for movement of NT) therefore cannot move chemicals into vesicles for pre-synaptic transmission exocytosis, resulting in signal not travelling, and therefore paralysis
- blocks release of Acetylcholine
If you block vesicle endocytosis, how would this affect release of small molecule vs peptide neurotransmitters?
block releases of small molecule NT (no vesicle recycling) but not peptides (secretory granules are ‘one and done’)
If AMPA receptors are permeable to both Na+ and K+, why does activating them cause depolarisation?
- receptors reverse potential is 0mV so opening channels move membrane potential closer to 0 (depolarised)
- at rest, membrane is only permeable to K+. even if you increase permeability to both Na+ and K+ (using an AMPA receptor,) Na+ permeability is proportionally higher than at rest
- by opening AMPA receptors, increasing relative permeability for Na+, compared to K+
What would happen if GABA opens a GABA-A receptor and membrane potential is below chloride’s Nernst potential? Would you get net inflow or outflow of chloride ions?
- if below Cl- Nernst Potential. opening chloride conductance depolarises cell (positive current going in, or negative currents go out)
- below Cl- Nernst potential, negative potential pushing Cl- out overwhelms concentration gradient pushing Cl- in
Why is atropine used to treat nerve gas poisoning?
- nerve gas Acetylcholine, by blocking Acetylcholinesterase
- atropine blocks muscarinic acetylcholine receptors
Why is an excitatory synapse on soma more effective in evoking AP in postsynaptic neuron than an excitatory synapse on tip of a dendrite?
- less distance to axon hillock
- EPSP decays as it propagates from tip of dendrite to soma
