Cellular Neuroscience Pt2 Flashcards
(190 cards)
0
Q
What is faster in electrophysiological analysis, many cells or single excitable cell?
A
single excitable cell (msec, sec)
1
Q
Neurophys has been a study of what?
A
electrical activity of the brain at the global and cellular level
2
Q
What does electrophysiological analysis of nervous system activity involve?
A
cathode ray oscilloscope recording of VOLTAGE-time displays
3
Q
Macro electrode are good for what?
A
population responses
4
Q
What are the diagnostic tools used for population responses?
A
- EEG, sEP, ERP (cortex & pathwways)
- compound whole nerve potential (peripheral nerve)
- EMG (group of muscle cells)
5
Q
What doe micro-electrodes record?
A
single cell responses
6
Q
What diagnostic tools are used for single cell recordings?
A
- single unit extracellular recording
- single unit Intracellular
- single unit patch-clamp
7
Q
what is an ERP?
A
event related potential for cell population recording
8
Q
what is an EEG?
A
electoencephalogram for recording potentials on the skull
9
Q
On a graph for ERP, EEG and WNP what is recorded on the y-axis upward
A
ERP - positive up
EEG - negative up
WNP - negative up
10
Q
in single unit recordings what charge is upward on y-axis?
A
positive up
11
Q
How are EEG used clinically?
A
diagnostic tool to tell abnormal from normal
identifies where pathology located
12
Q
What defines a normal EEG?
A
alpha rhythm average around midline
13
Q
What defines an abnormal EEG?
A
“spikes” in multiple leads
14
Q
**What is a problem with EEG?
A
the recording cannot tell us anything about what is wrong at the cellular level but can tell us grossly normal vs abnormal
15
Q
What are ERPs triggered by?
A
sensory input (visual, auditory, somato)
16
Q
What is receptotopic mapping?
A
map receptor sheets on to the brain (place-to-place mapping of r/c’s to cortex)
17
Q
****What are ERPs used for?
A
used to evaluate the general viability/functional integrity of a sensory pathway
18
Q
What are compound whole nerve potentials used for?
A
PNS electrodiagnosis
19
Q
What is important about graduated electrical stimulation of PNS recordings?
A
- smallest currents activate large fibers only
- large currents activate all fibers, small and large
20
Q
In thee PNS which fibers are myelinated and unmyelinated? what is their arrival during a CRO recording?
A
myelinated 1)Aalpha 2)Abeta 3)Adelta
unmyelinated 4) C
= order in which they appear in CRO
21
Q
What does a abnormal PNS recording look like?
A
-diabetes/MS => demyelination and inability to produce myelinating cells => increased lag time in AP
22
Q
***** What does peripheral neuropathy look like? significance of whole nerve potential?
A
- slowing, failure of conducting fibers
- doesnt tel what is happening at cellular level but rather what is happening with the nerve
23
Q
What are the functional/ clnical significance of EEGs, ERPs, WNP?
A
- oldest brain recording tech.
- excellent temporal, poor spatial res
- used for differential diagnosis of CNS, PNS, sk mm.
- inability to monitor cell-level processes
24
What are the benefits of single cell neurophysiology?
very fast electrical membrane communication (less than 1 sec)
25
What is involved in single unit electrophys?
plasma membrane
26
What are electrical membrane signalling directly and indirectly coupled to in single unit electrophys?
ion channels and signal transduction pathways
| Energy dependent
27
What type of potential do single unit recording have?
all-or-none
28
What encompass the graded potentials in a neuron and the electrogenic all or none membrane?
```
graded = dendrite and axon
all-or-none = axon
```
29
Are graded potentials passive or active?
passive electronic spread
30
Are all-or-none active or passive regenerative propagation?
active
31
What are some characteristics of functional dynamic polarization?
highly ATP dependent
| needs glucose & O2 to keep up (ionotropic = fast; melanotropic = slow)
32
What are the 3 tech. of single cell recording?
extracellular, intracellular unit recording & patch clamp
33
What is the resting membrane potential?
-70mV
34
What is important about patch-clamp?
single/group of ion channels
| - can be resting, graded, all-or-none
35
What is the physiological sequence via neuronal chains?
electrical => chemical => electrical...etc.
36
What did Sherrignton discover?
stop and go synapses
37
What is synaptic delay?
2msec for synaptic signal to move across synaptic cleft
38
What controls the actions at the synapse?
go (excitatory) and stop (inhibitory) messages
39
What is the importance of Go and Stop?
contraction and relaxation of mm groups etc
40
What kind of n.t. is Acetylcholine?
inhibitory
41
How do you quiet down striated mm?
quiet down CNS (Ach)
42
What is an excitatory amino acid?
glutamate
43
What is an inhibitory amino acid?
GABA
44
What is thee membrane of excitable cells permeable to?
lipid-soluble substances, NOT charged ions
45
A thin unit membrane acts as a good battery plate & stacks electrical charge, what does it show?
capacitance
46
Electrically charged entities can only get across membrane via what?
- slow crossing via transport proteins
| - rapidly via ion channels
47
Define leakage in p.m.
passive ion channels
always open
single ion selective
responsible for RMP or neurons, mm & glia
48
What are gated ion channels responsible for?
graded & all-or none AP for neurosecretion
49
What are the diffusional tendencies for Na, K, Cl, Ca?
Na, Cl, Ca = inward
| K = outward
50
How are conc. differences maintained with Na, Cl, Ca, K?
pumped by ion exchange
51
What are the tendencies of Na?
transport = Na-K pump
Intracellular conc = low
Ion diffusion = inward
52
What are the tendencies of K?
transport = Na-K pump
intracellular conc = high
ion diffusion = outward
53
What are the tendencies of Ca?
Transport = Ca pumps
intracell conc = low
ion diffusion = inward
54
What are the tendencies of Cl?
transport = KCC2 co transport
Intracell conc = low
ion diffusion = inward
55
What does KCC2 K-Cl cotransport involve?
1 K and 1 Cl => outside cell = K moving with conc gradient and Cl against
56
What forces act on ions dissolved in solution?
- diffusional
| - electrostatic
57
What is the electrochemical equilibrium?
diffusion stops when at equilibrium - dictated by NERNST equation
58
What is the rule for intracellular membrane voltage?
set closest to the equilibrium potential of the most permeant ion
- ion with the greatest # of open channels
59
What are the Eion for Ca, Cl, Na, K?
```
Ca = +246
Na = +60
Cl = -70
K = -90
```
60
What are the general features of RMP?
- always inside negative
| - found throughout the unit membrane but vary across types of excitable cells
61
What are the RMP of small, large neurons and mm, glial cells?
```
small = -60mV
large = -70mV
mm = -80mV
glial = -90mV
```
62
What is the significance of RMP?
* ***RMP in neurons & mm is the background against which all electrical signaling is produced
- glial cells have an RMP but do not generate electrical signals on cell membrane
63
What is the mechanism of RMP?
- RMP in glial cells is pure K diffusion potential
| - neurons & mm = predominantly K diffusion but Na ion inward leakage very small contribution
64
Is there a leakage channel for Ca in skeletal mm.?
NO
65
What is the importance of Na?
takes away negativity => establishes -70mV
66
What are the functions of leak current ion channels?
- single ion selective
- open at rest
- produce the resting membrane potential
67
What is the structure of leak current ion channels?
2 pore, 4 sided tetramere topolgy
68
Alpha and Beta proteins make up leak current ion channels, what is their function?
- alpha helix (4) form the channel
| - Beta form the anchoring protein
69
What are the importance of leak channels?
- expressed throughout entire excitable cell (K>Cl>Na)
| - produce RMP
70
What are depolarizing excitatory effects?
loss of polarization => positive and continuation of AP
71
What are the pathways of graded synaptic potentials?
ionotropic and metabotropic signal transduction pathways
72
What are the hyperpoarization inhibitory effects?
excess negativity (negative) => arrest the AP
73
What are the processes through which information is sent through a cell?
transduction -> transformation -> propagation -> translation
74
What are the membrane domains and associated electrical events in a cell?
dendrites & soma = graded, synaptic potentials
axon hillock, impulse trigger zone = all-or-none
axon = impulse propagation/conduction
axon terminals = excitation secretion coupling
75
Match the processes with the appropriate membrane domain
```
transduction = dendrites & soma
transformation = axon-hillock and impulse trigger zone
propagation = axon
translation = axon terminals
```
76
What happens when n.t release occurs at the synapse?
r/c binding => ion channels open or close => conductance change => postsynaptic potential changes => excited or inhibited postsynaptic cells
77
What are EPSPs?
excitatory postsynaptic potentials => voltage depolarization by excitatory n.t (neurotrophin), neuropeptide ligands, neuromodulator substance
78
What happens when 2 EPSPs elicited in rapid succession?
sum to produce a larger EPSP (temporal summation)
79
All excitatory synapses have 2 mechanisms, what are they?
ionotropic and metabotropic
80
What are all excitatory synapses calles?
Grey Type 1 synapses
81
What are some characteristics of Grey Type 1 Synapse (excitatory)?
- round presynaptic vesicles
- large presyn bulb with electron dense inside
- wide synaptic cleft
- dense postsyn basement membrane
- large extensive postsyn density
82
What are type 1 synapses known as beside Grey Type 1?
assymetrical junction
83
What are some functions, structure of ligand-gated ion channels?
- 1 pore, 4TM, 5 subunit pentameres
- gated open or closed by ligands
- especially like Na but selective to Cl, Ca, K too
84
What happens to the ligand-gated ion channel with glutamate presentation?
glutamate goes out = resting state = closed
| glutamate attaches = open
85
ligand - gated channels have 5 subunits, whats the importance?
selective filter
86
What did Sutherland discover?
- signalling molecules that control nerve cell function do so via 2 types of membrane signal transduction mechanisms: 1) IONOTROPIC 2) METABOTROPIC
87
WHat is direct/ ionotropic synaptic action?
- direct, selective binding of n.t. to surface r/c of ion channel
- rapid & reversible change in electrophysiology
- new addition to the cellular control arsenal
- ***OPEN or CLOSE membrane ion channels
88
What is the difference between ionotropic vs. metabotropic?
```
ionotropic = ligand gated ion channel
metabotropic = G protein coupled receptors
```
89
What is the system of activation for metabotropic r/c's?
nt => binds r/c => G-protein activated => effector protein => intracellular messengers => ion channel opens => ions flow across membrane
90
What is the special about indirect/ metabotropic synaptic action?
- slower & indirect
- G-protein/ P coupled
- turn on slowly => dephospo => turn off slowly
91
Where is the metabotropic motif commonly employed in?
the neural networks of the brain
92
What are CAMs?
cell-adhesion "docking" molecules which bind the cells together (ie. Neurexins & Neurligans)
93
What is the postsynaptic organization?
1) CAM
2) Ionotropic STPs
3) Metabotropic STPs
94
What is the AP threshold in a cell?
-65mV
95
What happens when EAA - Gutamate is introduced to ionotropic - STP?
- AMPA-r => open => increase conductance permeability => Increase Na in => Icrease EPSc => Graded Depol fast EPSP
96
What happens when EAA - Gutamate is introduced to metabotropic - STP?
mGlu-r => close => decrease conductance permeability => Decrease K out => Increase EPSc => Graded depol slow EPSP
97
What happens if the summation between iono and metabo STP is greater than or equal to 5mV above RMP (-70mV)?
trigger zone impulse and AP begins
98
What happens with channel opening?
Increased ionic permeability (Pion), Increased conductance (G), decreased membrane resistance (Rm)
99
What happens when a channel closes?
Decreased Pion, Decreased G, Increased Rm
100
What happens with an indirect closing of K metabo channel?
rebound depol postsyn (EPSP)
101
What happens with an indirect closing of sodium metabo channel?
rebound hyperpol postsyn (IPSP)
102
Metabo ion channel closing "gating themes"show passive decay, which is?
the excitatory voltages/currents die out as they move away from the postsyn membrane region
103
What happens to depol of postsyn membrane?
+ charges cancel out negative charge which causes a pushing effect away from postsyn membrane (see pg 58)
104
Why is the location crucial for testing electronic decay of graded EPSP?
the closer to the synapse = more powerful current; therefore the more powerful the message
105
What is temporal summation in a neuron?
repeated impulse over a short period of time from a cell produces temporal summation EPSCs/ EPSPs at that synapse
106
What is spatial summation in a neuron?
sensory summation that involves stimulation of several spatially separated neurons at the same time
107
If >5mV graded potential, what does this trigger at the AH-IS/T.Z areas?
Transformation = all-or-none AP
108
What are the characteristics of EPSPs?
- graded in size
- summate both temporally and spatially
- display passive electronic decay
109
At the axon hillock what happens to the signal in terms of graded synaptic membrane response?
transduced => transformed
110
What are IPSPs?
inhibitory postsyn potentials = hyperpolarize (SILENCE EFFECT)
111
What are the events from n.t release to postsyn excitation/inhibition?
nt release => r/c binding => ion channels open or close => conductance change (ion current flow) => post syn potential changes (EPSPs, IPSPs) => excited or inhibited postsyn cells
112
What can happen with 2 IPSPs elicited in rapid succession?
sum to produce a larger (-'ve) IPSP
113
What are Grey Type II Synapses?
inhibitory with IAA being GABAergic
114
Grey Type II Synapse are location specific, wher?
tend to cluster at specific locations toward axon hillock
115
What are some specifications of Inhibitory synapses?
- flattened oval presyn vesicles
- small, multiple presyn active zones
- narrow syn cleft
- modest postsyn basement membrane
- multiple, restricted postsyn densities
116
Are Inhibitory synapses asymmetrical?
NO, they are symmetrical (in terms of density)
| Grey type I are asymmetric
117
Where is the binding site on GABAa r/c Cl complex?
2 alpha subunits
118
All the ionotropic site is how many sided?
5 - ion selectivity because of this
119
What is the difference between Greys Type I and II in terms of ionotropic and metabotropic at active zone?
Greys Type II uses GABAa for both metabotropic and ionotropic and ionotropic are direct but slow!
120
Metabotropic signal transduction in Inhibitory synapses utilize what 2 GABA subtypes which correlate to which ions?
GABAb -> K (-90mV)
| GABAa -> Cl
121
How is the signal inhibitory when Cl- equilibrium is -70mV and GABAa is for above -70mV?
due to GABAb and the use of K efflux which equilibrium is -90mV (see pg 65) - essentially draws the equilibrium below -70mV
122
what is the neuropeptide for inhibitory synapses?
Eukephalin
123
What happens with GABA presentation for iono-STP?
GABAa => Increased conductance (open) => Increased Cl- IN => graded hyperpol FAST IPSP
124
What happens with GABA presentation for metabo-STP?
GABAb => Increased conductance (open) => Increased K+ OUT => graded hyperpol SLOW IPSP
125
Passive electronic decay for inhibitory synaptic voltages die out where?
prior to hillock, die out fast
126
IPSPs do what at the AH-IS trigger zone to suppress impulse production?
push voltages away from impulse threshold => postsyn inhibition
127
What happens if IPSP = EPSP; IPSP > EPSP; IPSP
IPSP = EPSP => cancel each other out and no AP
IPSP > EPSP => inhibitory effect (hyperpol) no AP
IPSP < EPSP => excitatory effect (depol) AP (>5mV)
128
What is neuronal integration?
IPSP + EPSP to determine whether an AP occurs
129
At the axon bulb what does the AP stimulate?
Ca to be released
130
What are the channels on the axon?
all or none impulse + voltage gated ion channel
131
What aa/nt stimulates excitatory actions? inhibitory? both?
```
excitatory = 75% Glutamate (E.A.A); 25% Ach, Adenosine, NA, serotonin
inhibitory = 90% GABAa/GABAb (I.A.A)
both = histamine, Ach
```
132
From threshold to peak what are the # in mV?
-65=>0=>+20
133
What is the Na dependent process in the all or none impulse?
rising depol phase
134
What is the K dependent process in the all or none impulse?
repol phase
135
What is the AP threshold?
-65mV
136
What causes the difference in AP from nerve to nerve?
axon hillock graded EPSP + summation time
137
What did Hodgkin and Huxley test on to prove ion movement through membrane pores?
squid giant axon
138
What causes the impulse that occurs at the TZ and subsequent opening of ion selective and voltage gated ion channels?
******positive, graded cationic generator currents supply the depolarizing voltage to trigger these events!
139
What happens when Na influx pushes charge inside the cell to positive?
inactivated state of r/c (AMPA) => refractory period
140
What happens when K efflux outside cell?
hyperpol. => cell need to repol to -90mV => refractory period
141
What is the spike freq upper limit?
800 spikes/sec
142
What can selectively block Na channel?
tetrodotoxin (TTX) & saxitoxin (STX)
143
What is saxidomus?
a specific toxin that inhibits depol of neuron (Na channel) therefore fatal to humans - from clams
144
What can selectively block K channels?
tetraethylammonium (TEA) from outside the cell & 4-Aminopyridine from inside after migration into the cell
145
Do the K and Na voltage gated channels differ in transmembrane segments?
No they both have 6TM, 1 pore and 4 sided tretramers
146
What is the difference between absolute and relative refractory periods?
absolute => no AP from second stimulus
| relative => second impulse fails to elicit an impulse of normal size or amplitude
147
What does the Na influx during thee rising depol phase of the AP spike produce?
local cationic (+) circuit current (LCC)
148
What is LCC?
helps to depol the next patch of membrane with Na voltage gated channels until reaches end of axon or fiber
149
What happens to the speed of conduction when you increase/ decrease axonal size in small, unmyelinated axons?
Increase axon size => decrease resistance => Increase speed of LCC => faster conduction velocity
Decrease axon size => increase resistance => decrease speed of LCC => slower conduction velocity
150
What is the conduction velocity in small unmyelinated axons?
0.3-4.0m/s
151
What is the conduction velocity of large myelinated axons?
5-120m/s
152
What is salidatory conduction? where does it take place at?
hopping conduction at the Nodes of Ranvier in myelinated axons
153
What are the characteristics of All-or-None Law?
- threshold voltage
- magnitude from threshold to peak voltage
- duration
- voltage waveform
- conduct/ propagate
- electrogenic -> self-regenerative
154
What does a high freq stimulation lead to in the axon bulb in terms of Ca?
general increase of Ca => release of peptide nt from large dense-core vesicles, as well as small molecule nt from small clear-core vesicles
155
What are stored in small vesicles in axon terminal?
small mol transmitter (glutamate, aspartate, GABA, Ach)
156
What is the sequence of events of AP arriving at axon terminal in terms of Ca?
AP => LCC opens Ca voltage gated channel => Increase in Ca => glutamate release => Glutamate bind to postsyn => Glutamate reuptake by glial cells or presyn cells
157
What is the Katz's Quantal Hypothesis of Transmitter Release?
- a single impulse forces many small vesicles to release their contents into synaptic cleft and then diffuse to postsyn and bind to recognition sites and open ligand-gated ion channels
158
What happens in silent chemical synapses, with no invading all or none impulse?
few "quanta" (small vesicles) release spontaneously and form a spontaneous miniature postsynaptic potential mPSP
159
What determines the amount of quanta released by the neuron?
Ca levels in the presynaptic terminal
160
where are neuropeptides generated and stored in a neuron?
generated in the neuron cell body from precursor molecules
| stored in large dense-core vesicles
161
What happens once the NP of a dense-core vesicle enters the synaptic cleft?
diffuses to the postsyn cell, the NP binds to a r/c/ which INDIRECTLY activates a signal transduction pathway and coupled postsynaptic cellular response
162
What happens to the NP in the synaptic cleft with decreased amounts of Ca?
the peptide diffuses out of the synaptic cleft
| altered by endopeptidases
163
What is Dales Rule?
a single neuron transcribes, constructs, packages, and releases the same chemical transmitter at ALL of its synaptic terminals (for both small and large vesicles)
164
What are the inhibitory NP for Glutamate and GABA?
Glu => Subs-P
| GABA => Enkephalin
165
Which r/c's do small molecule n.t. activate?
Iono & Metabo
166
What r/c's do NPs activate?
metabo ONLY!
167
Is there retrograde signalling with impulse-based signal release?
NO
168
What r/c's do non-impulse bases, continuous/constitutive signal release (growth factors) activate?
NGF, BDNF => Metabo-TrK-R
169
What are ways to terminate transmitter action?
- active transmitter re-uptake
- diffusion
- degradative processes
- autoreceptor inhibition of release
170
How are small molecule transmitters take up in the synaptic cleft? whats the effect?
- avid reuptake in glia & terminal via specific n.t. transporter
- rapid/fast decrease of conc. in the synaptic cleft which provides rapid termination of synaptic action
171
What Neuromodulator has different mechanism of termination of transmitter in the synaptic cleft than small molecule transmitter?
Ach = degradative enz - Ach-E in synaptic cleft
| Dopamine, serotonin, noradrenaline have same mech and effect as small molecule transmitter (Glu, Asp, GABA, Gly)
172
How are neuropeptides terminated in the synaptic cleft?
- ednopeptidases in synaptic cleft and diffusion
| - very slow breakdown and diffusion decreases # of NP in cleft - allows for prolonged action
173
What are special about autoreceptor actions in terms of n.t.?
provide negative feedback to decrease small mol n.t. release into snyaptic cleft - to stop synaptic action
- Glu comes back and binds to mGlu-R which inhibits release
- GABA binds to GABAb-R
174
What is presynaptic inhibition?
decrease n.t. release
175
What is presynaptic facilitation?
Increase n.t release
176
What is the mechanism of neuromodulation?
induced change in axon terminal Ca ion levels/ conc.
177
What n.t. is released from neuromusculare junctions?
Ach
178
Where is Ach released from in NMJ?
prejunctional component (active zone)
179
What are the 2 types of release from NMJ?
- spontaneous release
| - evoked release
180
Is an AP evoked with spontaneous release at NMJ?
- small depol of the post-junctional end plate region do not spread beyond the end-plate and do not excite the mm cell = NO!; however do produce mEPPs (miniature end plate potentials)
181
What is special about an EPP?
20-40mV with 1 release; graded response; very big and dont usually summate
182
Do evoked release at NMJ form an AP?
YES! form an EPP (end plate potential) which gives rise to an AP => tension generation
183
Is the NMJ Ca dependent?
YES!
184
How is Ach blocked?
ACh-E degrades Ach in cleft
185
****The motor end plate of the NMJ has specific characteristics, what are they?
- direct, ionotropic system
- nicotinic-Ach ion channel
- ligand gated ion channel
- 5 sided pentamer
186
What cause an End Plate Potentials (EPP)?
- binding of 2 Ach => gates open
- Increased conductance => depol
- large (20-40mV) event
- 2 ion voltage (Na influx (mostly) K efflux)
187
What are the characteristics of an NMJ?
- high-fidelity and high safety factor chemical synapse
| => obligatory and reliable 1-1 transmission of motorneuron impulse leads to mm impulse ("twitch")
188
What are special about electrical synapses in CNS?
- allows for unhindered passage of electrical ionic currents
- bidirectional communication
- mediates synchronized electrical activation of some cell types (neocortex, thalamus, brainstem (inhibitory) neurons, cardiac & smooth mm)
189
What is the structure of electrical synapses (gap junctions)?
6-seded hemi channels called connexons
| 4 alpha helixes per subunit
