Midterm 1 Flashcards
1
Q
What are the 3 germ layers of embryo?
A
Ectoderm (outer), mesoderm, endoderm (inner)
2
Q
What does ectoderm turn into?
A
Skin, neural tissue
3
Q
What does mesoderm turn into?
A
Muscles, bones
4
Q
What does endoderm turn into?
A
Internal organs
5
Q
What does the neural tube eventually turn into?
A
Brain and spinal cord
6
Q
Where does neural plate form?
A
Dorsal surface of ectoderm
7
Q
What is spina bifida?
A
Incomplete close of neural tube
8
Q
What can help prevent spina bifida?
A
Folic acid prenataly
9
Q
What causes synaptic delay?
A
Waiting for voltage channels to open, waiting for fusion and release of NT, waiting for diffusion and binding
10
Q
What are two types of receptors of post synaptic membrane?
A
Gpcr (metabotropic) ligand hated (ionotropic)
11
Q
What do neurotransmitter reiptake transporters do?
A
Remove NT from synaptic cleft so they. Sm be repackaged in vesicles
12
Q
Are ionotropic or metabotropic faster?
A
Ionotropic ( direct)
13
Q
How many subunits in ligand gated ion channel?
A
5, 2 alphas, beta, gamma, delta
14
Q
How many transmembrane (TM) domains does each subunit of a ionotropic receptor have?
A
4
15
Q
Which transmembrane domain forms the pore in ionotropic receptors?
A
M2
16
Q
What creates the ligand binding site in ionotropic receptors?
A
Extracellular N terminal domain
17
Q
How many tm domains do gpcr havr?
A
7 (no ion channels)
18
Q
What does extracellular site in metabotropic do? N or C terminus
A
Binds NT, N terminus
19
Q
What does intracellular site in metabotropic do? N or C terminus
A
Binds G protein, C terminus
20
Q
What are metabotropic receptors involved with?
A
Synaptic plasticity, learning and memory
21
Q
What class of enzymes add phosphate groups?
A
Kinases
22
Q
What class of enzymes remove phosphate groups?
A
Phosphatases
23
Q
How is de-phosphorylation regulated?
A
second messengers
24
Q
What are the steps of metabotropic receptors?
A
NT binds, g protein is activated, a subunit of g protein binds to effector protein, produces 2nd messenger (cAMP), activatrd PKA
25
What does PKA do?
phosphorylates ion channels, transcription factors, which activates calcium cchannels
26
What effect doess PKA phosphorylating ion channels have in cell?
Na+ ions flow into cell, changes membrane potential
27
What effect doess PKA phosphorylating transcription factors (ex. CREB) have in cell?
activates gene expression and cellular responses
28
Ca2+ entry into cell activates what specifically?
CaMK, which phosphorylates more TF's and causes more gene expression
29
What are some examples of CREB sensitive genes?
neurotrophin BDNF, tyrosine hydroxylase, immediate early genes
30
What does neurotrophin BDNF do?
promotes neuronal survival
31
What does tyrosine hydroxylase do?
catecholamine synthesis
32
What do immediate early genes do?
IEGs are implicated in learning and memory, and long term potentiation
33
When are thin and stubby spines more prevalent in brain?
immature brain
34
What is the most prevalent tye of dendritic spine?
mushroom
35
What are post synaptic densities composed of?
L-glutamate NT receptors
36
What does calcium effect in neurons?
membrane potential, release of NT, neurite growth and growth cone migration, regulates gene activity
37
What do EPSP result in?
depolarization via entry of Na+ ions
38
What do IPSP result in?
hyperpolarization via entry of Cl- ions
39
What are type 1 synapses?
excitatory, glutamergic, on dendrites, round vesicles
40
What are type 2 synapses?
inhibitory, gabaergic, on cell bodies, flat vesicles
41
What is spatial summation?
summation of inputs from multiple synapses
42
What is temporal summation?
summation of inputs from single synapse over timee
43
Where are gap junction found?
early embryonic stages, in brainstem, between astrocytes, some interneurons in cerebral cortex, thalamus, cerebellum, hypothalamus
44
What do gap junctions allow through them?
ions, molecular with large molecular weights, ATP, second messengers
45
What type of synaptic communciation is bidirectional?
electrical
46
Is electrical or chemcial synapses faster?
electrical
47
What are some problems with electrical synapses?
difficult to modulate the gating of channels, can't change signs (always flows downhill)
48
What are active zones?
sites of NT release
49
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
50
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
51
What type of synaptic transmission can change signs?
chemical
52
What is quanta?
amount of NT released frm a vesicle
53
Is the docking of synaptic vesicels reversible?
no
54
What are the eight steps of NT release and recycling?
1. NT are actively transported into vesicles
2. vesicles go in front of active zone
3. they dock
4. primed
5. Ca2+ causes fusion/pore opening
6. vesicles are taken up by clathrin coated pits
7. vesicels are reacidified and refilled with NT directly
8. also could be filled after passing through endosomal intermediate
55
What are the 3 SNARE proteins?
synaptobrevin, syntaxin, SNAP 25 (docking)
synaptotagmin (Ca2+ sensor)
56
What is the function of synaptotagmin?
Calcium snesor, regulates fast exocytosis at synapse
57
What do the 2 cytoplasmic domains of synaptotagmin do?
bind 5 Ca2+ ions
the affinity for calcium ions increases when vesicles bind to membranes
58
What does mutations in synaptotagmin cause?
loss of fast exocytosis
lethal
59
The priming of synaptic vesicles is dependent on what?
ATP
60
Why are NT stored in vesicles?
protection from degradation, sotrage system, concentration, regulation
61
There is a big difference in the concentration in cell, where is the concentration greater? (Calcium)
greater outside cell
less inside
62
When researchers injected a calcium buffer what did they find?
presynaptic current and postsynaptic response were gone
63
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
64
Is the pre/post synaptic terminals closer in electrical or chemical?
closer in electrical
65
What are excitable cellss?
can be stimualted to make an electrical current
muscle/nerves
66
Do only excitable cells have a resting potential?
no all cells do
67
What is the resting potnetial?
-70mV
68
What causes the resting potential?
Na+/K+ pump, leaky potassium channels
69
How much potassium and sodium is transported by the pump?
2 K+ in the cell and 3 Na+ out
net loss of positive charge
70
What is the ratio of the concentration of sodium ions?
outisde is 10x greater than inside
71
What is the ratio of the concentration of potassium ions?
inside is 20x greater than outisde
72
Electrical potentials are genarated across membrane of neurons because?
differences in concentrations of specific ions, membranes are selectively permeable to some ions
73
What allows ions to move agaisnt their concentration gradient?
ion transportors/pumps
74
What type of transportation does not need ATP?
ion channels
75
Are there more non gated Na or K channels?
more ungated K+ channels
(leaky channels)
76
At resting potential the membrane is more permeable to?
K+ ions
77
What can stimulate gated channels?
voltage, ligands binding, mechanical force like stretching
78
What does the Nernst equation predict?
equilibtium potential for a single ion
79
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
80
Each ions nernst calculation contributes to the memrbane potential, how is the size of the contribution weighted?
by the permeability of the ion
81
What does the goldman equation consider?
takes into acocunt the concentration gradient of the permeant ions and the relative permeability of the membrane ions
82
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
83
What are some types of voltage gated channels?
Na+, K+, Ca2+
84
What are some types of ligand gated channels?
nAChR, GABAaR, GluR, GlyR
85
Where are voltage gated channels found?
muslces and neuronal cells
86
How many subunits in Na+/Ca2+ channels?
4 homologous ones
87
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
88
Describe the structure of potassium voltage gated channel?
5 subunits, each repeated 4 times to form pore
89
Where is the inactivation gate located on voltage gateed channels?
N terminus
90
What is the voltage sensor made up of?
positively charge amino acids (arginine, lysine)
91
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
92
Why does voltage sensor rotate vertical during AP?
as membrane becomes positive it repels the amino acids in sensor
93
What is cell attacehd recording?
pipette makes contact with intact cell, measures current of single channel
94
What is inside out recording?
pipette attached to cel and then withdrawn the cytoplasmic side of channel is exposed, for single channel recording
95
What is microscopic current?
measuring current through single channel
96
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
97
Why is action potential initiated at axon hillock?
lower threshold, smaller diameter, higher desnity of Na+ channels, the Na+ channels here are slow inactivating
98
What is subthreshold stimuli?
stimuli that fail to elicit an action potential
99
What is all or none mean in reference to acction potential?
you either have an AP or not, no in between
100
What causes the refractory period?
inactivation of sodium channels
101
Do sodium or potassium channels open quicker?
sodium channels open faster
K+ is slow to open/close (helps restore resting potential)
102
What drives depolarization?
increase in permeability of Na+
103
What drives repolarization?
fall in permeability of na+ and K+
104
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
105
What is it called when an action potential can be triggered but needs stronger stimulus?
relatvie refractory period
106
How many genes for Na+ voltage gated channels?
at least 9
Nav 1.1-1.9
107
Where are Nav 1.2 channels located?
non myelinated axons
after myelination there is a loss of these channels
108
Where are Nav 1.6 channels located?
clustered at nodes of ranvier, only myelinated axons, not detecable under myelin
109
Do Na 1.2 or 1.6 channels have larger current?
1.6 does
110
What does the rate of conductance depend on?
passive and active flow of current, size (larger cells conduct faster), myelin, size of Na influx
111
Why do larger cells conduct faster?
becuase they have better passive flow
112
How fast do action potentials confuct down myelinated and unmeylinated?
0.5-10 m/s (umnyelin)
150 m/s (myelin)
113
Where is active cuurrent and passive current in myelinated axon?
active is nodes of ranvier
passive is under myelin
114
What is multiple sclerosis?
autoimmune, patches of demyelination in CNS
115
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)
116
What is the most common neurodegenerative disease of young adults?
multiple sclerosis
117
What gender is multiple sclerosis most common in?
women
also mainly affects caucasians
118
What is an example of a gene that causes MS?
MHC (on chromosome 6)
119
What are some environmental agents that cause MS?
measles, munmps, herpes, minerals, chemical agnets
120
What is MHC?
major histocompatibility complex
encode cell surface antigen presenting proteins
121
What is an epitope?
regions of proteins that can trigger a cellular immune response mediated by T or B cells
122
Which class of MHC is involved with MS?
Class II
123
Where is MHC Class II found?
on specialized antigen-presenting cellls (APCs) macrophages
124
Whaat do MHC Class II interact with?
CD4+ t cells (aka. helper t cells)
they divide rapidly and secrete cytokines that help immune response
125
Can white blood cells cross the BBB?
not in healthy people
they can in MS
126
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
127
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
128
What do cytokines do?
stimulate microglia/astrocytes, recruit macrophages and B cells, make more cytokines and antibodies
129
Why does partial recovery happen in MS?
there is an increase in the number of channels along the unmyelianted part
more Na1.2
130
Why is there increased intra axonal Ca2+ in MS?
because there are more Na/Ca exchangerss
131
How are myelin/axons damaged in MS?
cytokines, B cells, direct complement activation, increased Ca2+, increase of free radicals, nitric oxide formation
132
Does remyelination happen?
yes but limited, usually myelin is thinner and shorter internodes
133
What allows remyelination to happen?
oligodendrocyte precursor cells, neural precursor cells, stem cells
134
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
135
Demyelination-induced axon loss is?
irreversible
136
What causes the progressive disability in MS?
axon damage and degeneration along with neuron loss (brain atrophy)
137
What are the four types of MS?
benign, relapsing-remitting, secondary-progressive, primary progressive
138
What does benign MS look like?
stable, gets worse goes back to stable and repeats
139
What does relapsing-remitting MS look like?
stable and then gets worse , goes back to stable but slightly worse basline, repeats
140
What does secondary progressive MS look like?
like relapsing remitting but then it becomes steaadly progressive
141
What does primary progressive MS look like?
starts off and continuously gets worse (10-20%)
142
What are attacks called in MS? What are they preceeded by?
relapses
can be unpredicatble or after trigers like cold or stress
143
What is thee most common type of MS?
relapsing-remitting 85-90%
144
What type of MS causes the most disability?
secondary progressive
145
What type of MS mainly presents in people who get it later in life?
primary progressive
146
What in the oligodendrocyte membrane are recognized as foregin by T cells?
MBP, MOG, MAG
147
How can MS be diagnosed?
MRI, testing CSF, visual evoked potentials and somatosensory evoked potentials
148
What do MRI look like in people with MS?
bright lesions show demyelination, widened lateral ventricles and cortical sulci
149
How does testing CSF show MS?
testd for oligoclonal bands which are immunoglobulins (evidence for chronic inflammation)
150
How do VEPs and SEPs show MS?
electrical potnetial is recorded after stimulus, people w/MS respond less actively
151
Where are plaques in MS found most likely?
optic nerves, brainstem, cerbellum, spinal cord
152
What forms plaques in MS?
macrophages containing undigest myelin, axonal debris, microglia
153
What is the most common symptoms of initail attack in MS?
change in sensation to face/arms/legs
154
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
155
15 years after diangosis how many people need assistnace?
50-60%
156
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
157
What is a difficulty with the treatment option of steem cells with MS?
need to implant stem cells in are with damage
158
What is beta interferon?
treatment for relasping-remitting MS, given by subcutaneous injections, glycoproteins with antivirl action, reduces # and severity of relapses
159
What does the synthetic form of myelin basic protein do?
inhibits the binding of self MBP to the T cells
160
What are some possible therpies for MS?
immunosuppresant, glucocorticoids, antioxidant therapy, antidepressants, muscle relaxants, tranquilizers
