Midterm 1 Flashcards
What are the 3 germ layers of embryo?
Ectoderm (outer), mesoderm, endoderm (inner)
What does ectoderm turn into?
Skin, neural tissue
What does mesoderm turn into?
Muscles, bones
What does endoderm turn into?
Internal organs
What does the neural tube eventually turn into?
Brain and spinal cord
Where does neural plate form?
Dorsal surface of ectoderm
What is spina bifida?
Incomplete close of neural tube
What can help prevent spina bifida?
Folic acid prenataly
What causes synaptic delay?
Waiting for voltage channels to open, waiting for fusion and release of NT, waiting for diffusion and binding
What are two types of receptors of post synaptic membrane?
Gpcr (metabotropic) ligand hated (ionotropic)
What do neurotransmitter reiptake transporters do?
Remove NT from synaptic cleft so they. Sm be repackaged in vesicles
Are ionotropic or metabotropic faster?
Ionotropic ( direct)
How many subunits in ligand gated ion channel?
5, 2 alphas, beta, gamma, delta
How many transmembrane (TM) domains does each subunit of a ionotropic receptor have?
4
Which transmembrane domain forms the pore in ionotropic receptors?
M2
What creates the ligand binding site in ionotropic receptors?
Extracellular N terminal domain
How many tm domains do gpcr havr?
7 (no ion channels)
What does extracellular site in metabotropic do? N or C terminus
Binds NT, N terminus
What does intracellular site in metabotropic do? N or C terminus
Binds G protein, C terminus
What are metabotropic receptors involved with?
Synaptic plasticity, learning and memory
What class of enzymes add phosphate groups?
Kinases
What class of enzymes remove phosphate groups?
Phosphatases
How is de-phosphorylation regulated?
second messengers
What are the steps of metabotropic receptors?
NT binds, g protein is activated, a subunit of g protein binds to effector protein, produces 2nd messenger (cAMP), activatrd PKA
What does PKA do?
phosphorylates ion channels, transcription factors, which activates calcium cchannels
What effect doess PKA phosphorylating ion channels have in cell?
Na+ ions flow into cell, changes membrane potential
What effect doess PKA phosphorylating transcription factors (ex. CREB) have in cell?
activates gene expression and cellular responses
Ca2+ entry into cell activates what specifically?
CaMK, which phosphorylates more TF’s and causes more gene expression
What are some examples of CREB sensitive genes?
neurotrophin BDNF, tyrosine hydroxylase, immediate early genes
What does neurotrophin BDNF do?
promotes neuronal survival
What does tyrosine hydroxylase do?
catecholamine synthesis
What do immediate early genes do?
IEGs are implicated in learning and memory, and long term potentiation
When are thin and stubby spines more prevalent in brain?
immature brain
What is the most prevalent tye of dendritic spine?
mushroom
What are post synaptic densities composed of?
L-glutamate NT receptors
What does calcium effect in neurons?
membrane potential, release of NT, neurite growth and growth cone migration, regulates gene activity
What do EPSP result in?
depolarization via entry of Na+ ions
What do IPSP result in?
hyperpolarization via entry of Cl- ions
What are type 1 synapses?
excitatory, glutamergic, on dendrites, round vesicles
What are type 2 synapses?
inhibitory, gabaergic, on cell bodies, flat vesicles
What is spatial summation?
summation of inputs from multiple synapses
What is temporal summation?
summation of inputs from single synapse over timee
Where are gap junction found?
early embryonic stages, in brainstem, between astrocytes, some interneurons in cerebral cortex, thalamus, cerebellum, hypothalamus
What do gap junctions allow through them?
ions, molecular with large molecular weights, ATP, second messengers
What type of synaptic communciation is bidirectional?
electrical
Is electrical or chemcial synapses faster?
electrical
What are some problems with electrical synapses?
difficult to modulate the gating of channels, can’t change signs (always flows downhill)
What are active zones?
sites of NT release
What are the steps of chemical synaptic transmission?
NT are made and stored, action potential arrives, depolarization opens voltage gated channels, influx of Ca2+, NT is released via exocytosis, NT binds to receptor, causes EPSP or IPSP, removal of vesicle via endocytosis
What are the three criteria for something to be a neurotransmitter?
must be made and present in presynaptic terminal, must be released in response to depolarization and be Ca2+ dependent, must be a specific receptor, mut be mehcnaism to remove, effects are reproduced by known agonists
What type of synaptic transmission can change signs?
chemical
What is quanta?
amount of NT released frm a vesicle
Is the docking of synaptic vesicels reversible?
no
What are the eight steps of NT release and recycling?
- NT are actively transported into vesicles
- vesicles go in front of active zone
- they dock
- primed
- Ca2+ causes fusion/pore opening
- vesicles are taken up by clathrin coated pits
- vesicels are reacidified and refilled with NT directly
- also could be filled after passing through endosomal intermediate
What are the 3 SNARE proteins?
synaptobrevin, syntaxin, SNAP 25 (docking)
synaptotagmin (Ca2+ sensor)
What is the function of synaptotagmin?
Calcium snesor, regulates fast exocytosis at synapse
What do the 2 cytoplasmic domains of synaptotagmin do?
bind 5 Ca2+ ions
the affinity for calcium ions increases when vesicles bind to membranes
What does mutations in synaptotagmin cause?
loss of fast exocytosis
lethal
The priming of synaptic vesicles is dependent on what?
ATP
Why are NT stored in vesicles?
protection from degradation, sotrage system, concentration, regulation
There is a big difference in the concentration in cell, where is the concentration greater? (Calcium)
greater outside cell
less inside
When researchers injected a calcium buffer what did they find?
presynaptic current and postsynaptic response were gone
What are the four main roles of calcium?
contributes to electrical prperties of neurons by changing membrane potential, release of NT, neurite outgrowht and growht cone migration, regulates geene activity
Is the pre/post synaptic terminals closer in electrical or chemical?
closer in electrical
What are excitable cellss?
can be stimualted to make an electrical current
muscle/nerves
Do only excitable cells have a resting potential?
no all cells do
What is the resting potnetial?
-70mV
What causes the resting potential?
Na+/K+ pump, leaky potassium channels
How much potassium and sodium is transported by the pump?
2 K+ in the cell and 3 Na+ out
net loss of positive charge
What is the ratio of the concentration of sodium ions?
outisde is 10x greater than inside
What is the ratio of the concentration of potassium ions?
inside is 20x greater than outisde
Electrical potentials are genarated across membrane of neurons because?
differences in concentrations of specific ions, membranes are selectively permeable to some ions
What allows ions to move agaisnt their concentration gradient?
ion transportors/pumps
What type of transportation does not need ATP?
ion channels
Are there more non gated Na or K channels?
more ungated K+ channels
(leaky channels)
At resting potential the membrane is more permeable to?
K+ ions
What can stimulate gated channels?
voltage, ligands binding, mechanical force like stretching
What does the Nernst equation predict?
equilibtium potential for a single ion
What is the Nernst equation? What do the variables stand for?
58/z log[x]o/[X]i
z is the charge of ion
[X] is concentration of ion inside and outside
Each ions nernst calculation contributes to the memrbane potential, how is the size of the contribution weighted?
by the permeability of the ion
What does the goldman equation consider?
takes into acocunt the concentration gradient of the permeant ions and the relative permeability of the membrane ions
What is the goldman equation?
= RT/F ln P[X]o/P[X]i
if ion is negative flip the division so inside over outside instead
add the different divisions together
What are some types of voltage gated channels?
Na+, K+, Ca2+
What are some types of ligand gated channels?
nAChR, GABAaR, GluR, GlyR
Where are voltage gated channels found?
muslces and neuronal cells
How many subunits in Na+/Ca2+ channels?
4 homologous ones
How many transmembrane domains in each subunit of Na+/Ca2+ channels?
Which one is voltage sensor, which form pore?
6 (S1-S6)
S4, S5 and S6
Describe the structure of potassium voltage gated channel?
5 subunits, each repeated 4 times to form pore
Where is the inactivation gate located on voltage gateed channels?
N terminus
What is the voltage sensor made up of?
positively charge amino acids (arginine, lysine)
Why does voltage sensor lay flat closing pore at rest?
positvely charged amino acids are attracted to residues of S2 and S3 and negatviely charged inner membrane
Why does voltage sensor rotate vertical during AP?
as membrane becomes positive it repels the amino acids in sensor
What is cell attacehd recording?
pipette makes contact with intact cell, measures current of single channel
What is inside out recording?
pipette attached to cel and then withdrawn the cytoplasmic side of channel is exposed, for single channel recording
What is microscopic current?
measuring current through single channel
What can the patch clamp determine?
the molecular composition of ion channels, when signle ion opens/closes, changes in configuration upon opening/closing, channel specificty
Why is action potential initiated at axon hillock?
lower threshold, smaller diameter, higher desnity of Na+ channels, the Na+ channels here are slow inactivating
What is subthreshold stimuli?
stimuli that fail to elicit an action potential
What is all or none mean in reference to acction potential?
you either have an AP or not, no in between
What causes the refractory period?
inactivation of sodium channels
Do sodium or potassium channels open quicker?
sodium channels open faster
K+ is slow to open/close (helps restore resting potential)
What drives depolarization?
increase in permeability of Na+
What drives repolarization?
fall in permeability of na+ and K+
Why does the hyperpolarization phase happen?
K+ channels take longer to clsoe, so more K+ is leaving the cell than normal, so it gets more neagtive
What is it called when an action potential can be triggered but needs stronger stimulus?
relatvie refractory period
How many genes for Na+ voltage gated channels?
at least 9
Nav 1.1-1.9
Where are Nav 1.2 channels located?
non myelinated axons
after myelination there is a loss of these channels
Where are Nav 1.6 channels located?
clustered at nodes of ranvier, only myelinated axons, not detecable under myelin
Do Na 1.2 or 1.6 channels have larger current?
1.6 does
What does the rate of conductance depend on?
passive and active flow of current, size (larger cells conduct faster), myelin, size of Na influx
Why do larger cells conduct faster?
becuase they have better passive flow
How fast do action potentials confuct down myelinated and unmeylinated?
0.5-10 m/s (umnyelin)
150 m/s (myelin)
Where is active cuurrent and passive current in myelinated axon?
active is nodes of ranvier
passive is under myelin
What is multiple sclerosis?
autoimmune, patches of demyelination in CNS
What are some symptoms of multiple sclersis?
weakness and clumsiness, stiffness/gait disturbances, visual defects, mental defects (lack of judgement, emotional liability, sudden weeping/laughter)
What is the most common neurodegenerative disease of young adults?
multiple sclerosis
What gender is multiple sclerosis most common in?
women
also mainly affects caucasians
What is an example of a gene that causes MS?
MHC (on chromosome 6)
What are some environmental agents that cause MS?
measles, munmps, herpes, minerals, chemical agnets
What is MHC?
major histocompatibility complex
encode cell surface antigen presenting proteins
What is an epitope?
regions of proteins that can trigger a cellular immune response mediated by T or B cells
Which class of MHC is involved with MS?
Class II
Where is MHC Class II found?
on specialized antigen-presenting cellls (APCs) macrophages
Whaat do MHC Class II interact with?
CD4+ t cells (aka. helper t cells)
they divide rapidly and secrete cytokines that help immune response
Can white blood cells cross the BBB?
not in healthy people
they can in MS
What happens during the inflammartory stage of MS?
initial infection happens and is processed by macrophages, they display the antigen with MHC molecules, this is recgonized by t cells which activates th1 cells in blood, travel to CNS and encounter local APCs which display a self antigen, reactivates th1 cells which secrete cytokines
How are th1 cells able to cross BBB in MS?
travel from blood to BBB, bind to adhesion molecules on surface of BBB endothelium, secrete proteases that breakdown the BBB
What do cytokines do?
stimulate microglia/astrocytes, recruit macrophages and B cells, make more cytokines and antibodies
Why does partial recovery happen in MS?
there is an increase in the number of channels along the unmyelianted part
more Na1.2
Why is there increased intra axonal Ca2+ in MS?
because there are more Na/Ca exchangerss
How are myelin/axons damaged in MS?
cytokines, B cells, direct complement activation, increased Ca2+, increase of free radicals, nitric oxide formation
Does remyelination happen?
yes but limited, usually myelin is thinner and shorter internodes
What allows remyelination to happen?
oligodendrocyte precursor cells, neural precursor cells, stem cells
What inhibits remyelination in MS?
loss of oligodendrocytes and OPCs, inhibitory signals by inflammation, obstruction of oligodendrocytes by astrocytic scars, inhibitory signals between axonal proteins
Demyelination-induced axon loss is?
irreversible
What causes the progressive disability in MS?
axon damage and degeneration along with neuron loss (brain atrophy)
What are the four types of MS?
benign, relapsing-remitting, secondary-progressive, primary progressive
What does benign MS look like?
stable, gets worse goes back to stable and repeats
What does relapsing-remitting MS look like?
stable and then gets worse , goes back to stable but slightly worse basline, repeats
What does secondary progressive MS look like?
like relapsing remitting but then it becomes steaadly progressive
What does primary progressive MS look like?
starts off and continuously gets worse (10-20%)
What are attacks called in MS? What are they preceeded by?
relapses
can be unpredicatble or after trigers like cold or stress
What is thee most common type of MS?
relapsing-remitting 85-90%
What type of MS causes the most disability?
secondary progressive
What type of MS mainly presents in people who get it later in life?
primary progressive
What in the oligodendrocyte membrane are recognized as foregin by T cells?
MBP, MOG, MAG
How can MS be diagnosed?
MRI, testing CSF, visual evoked potentials and somatosensory evoked potentials
What do MRI look like in people with MS?
bright lesions show demyelination, widened lateral ventricles and cortical sulci
How does testing CSF show MS?
testd for oligoclonal bands which are immunoglobulins (evidence for chronic inflammation)
How do VEPs and SEPs show MS?
electrical potnetial is recorded after stimulus, people w/MS respond less actively
Where are plaques in MS found most likely?
optic nerves, brainstem, cerbellum, spinal cord
What forms plaques in MS?
macrophages containing undigest myelin, axonal debris, microglia
What is the most common symptoms of initail attack in MS?
change in sensation to face/arms/legs
What are some congitive impairments in MS?
difficulty performing multiple tasks at once, toruble following detailed instructions, loss of short term memory, emotional instability, fatigue
15 years after diangosis how many people need assistnace?
50-60%
What are some challenges with potential treatments for MS?
CNS axons dont have regenartive capabilties, formation of glial scar, presence of myelin associated inhibitory molecules
What is a difficulty with the treatment option of steem cells with MS?
need to implant stem cells in are with damage
What is beta interferon?
treatment for relasping-remitting MS, given by subcutaneous injections, glycoproteins with antivirl action, reduces # and severity of relapses
What does the synthetic form of myelin basic protein do?
inhibits the binding of self MBP to the T cells
What are some possible therpies for MS?
immunosuppresant, glucocorticoids, antioxidant therapy, antidepressants, muscle relaxants, tranquilizers
