Neuro Elmsie Flashcards
(200 cards)
1
Q
Membrane potential is directly generated by the activity of….
A
ion channels
2
Q
The force that controls movements of ions across the plasma membrane is the…
A
electrochemical gradient
3
Q
What are some non-selective ligand gated ion channels?
A
nicotinic ACh channel glutamate (AMPA and NMDA) channels
4
Q
GABA channel is a selective ligand-gated ion channel for …
A
Cl-
5
Q
In order for a cell to have a membrane potential, it must have …
A
a Na+ ion gradient across the plasma membrane
6
Q
Resting Membrane Potential is usually about
A
-70mV
7
Q
There are ionic pores filled with water in lipid membranes that allow the hydrophilic ions to pass through the hydrophobic membrane. To make one of these ion pores selective, what happens?
A
amino acids line the pore - glutamate is negative, so it attracts Ca2+ and repels Cl- lysine and arginine are positive, so it attracts Cl-
8
Q
A charged amino acid, separate from those in an ionic pore, to aid in controlling membrane potential could form the channel’s… this sits on the inside of the membrane at rest
A
voltage-sensor
9
Q
Upon depolarization, the voltage sensor is repelled outward, causing
A
movement that causes the channel to open
10
Q
At rest, what are the activation gate and inactivation gate doing in regard to ionic gates/channels?
A
activation gate is closed inactivation gate is open
11
Q
With depolarization, the activation gate…
A
opens rapidly to allow ion movement
12
Q
With depolarization, the inactivation gate…
A
closes slowly so channel remains open during depolarization and channels accumulate in the inactive state
13
Q
One effect of hyperpolarization of voltage-dependent Na+ channels is to…
A
open the inactivation gate
14
Q
How do Calcium Channel Blockers work in regards to voltage-gated ion channels? What channel do they work on specifically?
A
enhance the inactivation of channels Cav1.2 tp arterial smooth muscle
15
Q
Ligand-gated channels have their gate located…
A
at the narrowest portion of the pore, usually the very middle
16
Q
Analogous to inactivation, for ligand channels, this causes closure of the channel.
A
desensitization - constant presence of activating ligand
17
Q
The balance of electrical and chemical forces creates the… of the membrane/cell
A
equilibrium potential
18
Q
Equilibrium potential is determined by…
A
charge of the ion and concentration of ions across the membrane
19
Q
Low intracellular Na+ and low extracellular K+ is maintained by..
A
Na-K ATPase
20
Q
What allows Ca2+ to be an intracellular messenger?
A
exquisite low level and control inside cell, by CaATPase
21
Q
What is the primary channel responsible for RMP (resting membrane potential)?
A
K2p (2-pore K channel)
22
Q
What increases activity of K2p? What does this result in?
A
heat, acidic pH, and pressure resulting in hyperpolarization
23
Q
Membrane potential becomes more positive (depolarizing) with K+ doing what?
A
K+ increasing extracellularly
24
Q
Equilibrium potentials of K+ Na+ Cl- Ca2+ HCO3-
A
K -86 Na 58 Cl -78 Ca 125 HCO3 -12
25
Which ion channel dominates conductance at the peak of AP?
Na+
26
The AP repolarization phase is primarily driven by...
Nav channel inactivation
27
Kv opening is slow relative to Nav so peak K+ efflux occurs...
during repolarization
28
Kv transiently hyperpolarizes the membrane potential after the AP. This is called...
afterhyperpolarization
29
immediately following an AP, what percent of Nav are inactivated?
90%
30
Kv channels (except K2p) are closed at rest and remain closed during....
depolarization, so Na+ influx is unopposed
31
What direction does K+ always move?
always moving OUTWARD through Kv
32
A depolarized RMP does what to Nav availibility?
decreases
33
Hyperkalemia causes the RMP to... ultimately doing what?
depolarize, causing AP generation to fail
34
Nav channels are sensitive to what toxin from puffer fish? Is there an exception?
sensitive to TTX - tetrodotoxin Nav1.5 - heart (and maybe 1.8 and 1.9 -pain) could be resistant to the toxin
35
Someone with a mutation in what Nav channel might never feel pain? If this is a gain of function mutation, what would happen?
Nav1.7 person in chronic pain
36
All Nav channels, except...., are involved in AP generation by providing Na influx for depolarization. This other channel is unique because...
Nav1.9 it activates too slowly to be part of Na influx but activates at a more negative voltage
37
If a pt has a neuroma, what channels might be upregulated, causing the pt more pain?
Nav1.8 and Nav1.9
38
What Cav acts as voltage sensors to trigger Ca2+ release from sarcoplasmic reticulum in skeletal muscle?
Cav1.1
39
What is the primary target of calcium channel blockers?
Cav1.2 (role in neuronal excitability, but no role in NT release, so CCB do not alter NT)
40
Cav1.3 channel affects...
neurons and cardiac cells in pacemaking - SA and AV nodes
41
What channel is responsible for all synaptic terminals in the CNS, Ca2+ to trigger NT release at presynaptic NMJ?
Cav2.1
42
Cav2.2 channels are present at all synaptic terminals in the CNS, having less influence on synaptic release, but more geared toward...
sympathetic and pain sensory
43
What drug inhibits Cav2.2 to treat chronic pain? How is it delivered?
Ziconotide intrathecal delivery
44
What channel is in charge of rhythmic electrical activity in the SAN and CNS?
Cav3 SAN also Cav1.3
45
Cav1 and Cav2 have auxillary subunits to modify their gating. What do Cavbeta subunits do?
move Cav1 and Cav2 from ER to plasma membrane - regulate membrane levels of Cav - alter speed of inactivation
46
Cav1 and Cav2 have auxillary subunits to modify their gating. What do Cav-alpha2-delta subunits do?
move Cav1 and Cav2 from ER to plasma membrane - shift voltage dependence of channel activation - increase activity with chronic nerve injury
47
What is the target of gabapentin and pregablin drugs?
Cav-alpha2-delta subunit of Cav1 and Cav2
48
Increasing K+ channel activity will...
decrease neuronal or muscle electrical excitability
49
Anesthesia/volatile anesthetic agents (like sevoflurane) target what channel in order to do what?
target K2p in order to hyperpolarize neurons
50
Calcium can activate some K+ channels (Kca) during the AP. This Kca channel helps to ...
repolarize the neurons and help produce afterhyperpolarization - sets the number and frequency of APs during burst
51
Increased Kca channel activity will do what to AP frequency?
decrease
52
What might inhibit Kca channels, resulting in an increase in AP frequency?
Apamin - bee venom toxin
53
What K+ channel helps to hold the membrane potential near RMP?
Inward-rectifying K+ channel (Kir)
54
What sets the membrane potential between AP in the heart?
Kir
55
Activation of GIRK channels by ACh receptors in cardiac muscle (vagal input) causes what to happen?
HR to slow
56
What drug is used in MS to inhibit non-specific Kv channels? How does this work?
4-aminopyridine - blocks Kv in demyelinated axons to increase AP conduction and improve coordination
57
What channels does the drug amiodarone block?
Kv11 (Ikr?), Nav1.5, and Cav1.2
58
What drug activates Kv7 at myelinated axons at the nodes of ranvier to decrease electrical activity and is used as an anti-epileptic?
Ezogabine
59
What is the major excitatory NT in the CNS?
glutamate
60
What channels are fast, excitatory synaptic transmission?
AMPA
61
NMDA channels require what two things to be active?
1.glutamate and glycine binding at separate sites 2. previous depolarization of AMPA channel
62
What does depolarizing AMPA channel have to do with NMDA?
depolarized AMPA channel repels Mg2+ that normal blocks NMDA channel, allowing influx of Na+ and Ca2+
63
What does NMDA channel do in the big picture of function?
drives neuronal plasticity involved in learning and memory
64
What drugs block NMDA channels and why would they be used?
- ketamine - anesthesia - memantine - Alzheimer's
65
What is the major inhibitory NT in the CNS?
GABA
66
Epilepsy can be induced by blocking which ligand-gated channel?
GABAa
67
TRPA channels, with gene TRPA1 are found at sensory nerve terminals and respond to what stimulus?
painful response to mustard oil, wasabi, or tear gas (acrolein), burning of propofol, extreme cold
68
TRPV channels, esp TRPV1 are activated by... When might they be a target of a drug?
noxious heat and capsaicin - drug target for pain management, such as capsaicin transdermal patch to desensitize nociceptors
69
TRPM channels, esp TRPM8 is activated by...
methanol, cool sensation - signaling cold temp to CNS
70
In .... propagation, amplitude of the electrical signals do not change with distance from the source and participate as "....."
active all or none there is a threshold for generation
71
amplitude decreases as it gets farther from its source is part of...
passive propagation
72
Nav channels in the active zone are...
activated
73
Active propagation along axons requires..
Nav channels
74
In the refractory zone, some Kv channels are ...
open
75
What is the gating process that causes APs to annihilate each other when they meet in an axon?
Nav channel inactivation (refractory zones that follow APs)
76
synaptic input activated multiple times in a short period would be considered .... and occurs with (passive/active) electrical signals?
temporal summation passive electrical signals
77
simultaneous activation of multiple inputs would be considered... and occurs in passive electrical signals.
spatial summation
78
What are synaptic potentials?
EPSP and IPSP traveling along dendrite to soma
79
Why does amplitude of electrical signal decrease with distance from the source in passive propagation?
loss/leak of current along the membrane depending on 1. axial resistance 2. membrane resistance
80
If the diameter of an axon increases, then the resistance of that axon will...
decrease
81
If there is a higher membrane resistance of an axon, what will happen to the electrical signal? What creates membrane resistance?
less leaking, goes farther - created by myelination from Schwann cells in PNS and Oligodendrocytes in CNS
82
In myelinated axons, Nav channels are found only ...
at Nodes of Ranvier
83
Where are Kv channels in myelinated axons? How do they work?
buried in myelin - non-functioning in healthy humans, but as demyelinating disease occurs, Kv channels are exposed and will slow AP propagation
84
In healthy pt, a myelinated axon with an AP is only repolarized by what channels?
Nav inactivation and K2p activation
85
small diameter unmyelinated axons have lower AP conduction velocity compared to large myelinated axons because...
the distance that passively propagated positive current spreads is shorter
86
What is determined by the number of active channels opposing depolarization vs. driving depolarization?
AP threshold
87
What is the mechanism holding the absolute refractory period?
Nav channel inactivation mostly - some activity of Kv following APs are generated in unmyelinated axons and neuronal cell bodies
88
a frequency decreasing with continued application of a stimulus would be considered... How does this work?
accomodation/adaptation - build up of inactivated Nav channels and activated Kv channels with each AP so strong that AP can be terminated while stimulus is still applied
89
What K+ channel is too slow to participate in AP repolarization? What does the channel do instead?
Kv7 - regulate excitability by 1. some open and help set RMP 2. can help terminate a burst
90
Mutation in Kv7 gene can result in ... What drug targets Kv7 channel (increasing K+ efflux across neuronal membrane) to combat this?
epileptic seizures - Ezogabine
91
for a subthreshold stimulus, the membrane potential is repolarized by the activity of...
K2p channels
92
What structures are used by neurons to receive input from other neurons?
both soma and dendrite
93
AP invades synaptic terminal and activates what channels that will open a pathway for Ca2+ influx into synaptic terminal?
Cav2 channels
94
Ca2+ influx into synaptic terminals will bind to
vesicle docking proteins
95
The binding of Ca2+ and vesicle docking proteins in the presynaptic terminal will cause...
fusion of synaptic vesicle with presynaptic membrane, ultimately releasing stored NT into the cleft
96
NT will cross the cleft and bind to and activate receptors/ion channels to generate...
PSP - post-synaptic potential (either EPSP or IPSP)
97
How are most NTs removed from the cleft?
transport proteins
98
Tricyclic antidepressants treat depression by...
blocking serotonin reuptake
99
Botulinum toxin produce their clinical effect at the NMJ by...
destroying presynaptic vesicle docking proteins
100
Fast synaptic transmission occurs via a combo receptor and channel put into 1 protein. They are called Ionotropic receptors. Examples are...
excitatory - glutamate -\> AMPA and NMDA channels - ACh -\> nicotonic receptors inhibitory - GABA -\> GABAa - glycine -\> glycineR
101
Slow synaptic transmission goes through..
GPCRs or metabotropic receptors
102
What is the primary effect of GIRK?
inhibiting neuronal activity, like in opioids
103
Cav2 channels are inhibited by... to inhibit AP signaling by suppressing Ca2+ influx; it inhibits excitatory NT release, even excitatory when inhibiting GABA
Beta gamma subunit of GPCRs
104
Ketamine blocks what channel?
NMDA
105
Valium enhances what channel?
GABA
106
Morphine inhibits pain by bindign to mu-opioid receptors that results in
inhibition of presynaptic glutamate release
107
inhibitory synapses are primarily found on the...
soma
108
summation of EPSPs enough for AP generation at axon hillocks are considered...
synaptic integration
109
IPSP can cancel out EPSP through ....
spatial summation
110
If GABAa is inhibited by IPSPs (perhaps by picrotoxin), it will cause...
epilepsy
111
What does picrotoxin do?
reduces membrane Cl- conductance, causing IPSPs to inhibit GABAa
112
What would you give to terminate seizures?
midazolam
113
In healthy muscle, an AP in a motor neuron will...
always elicit contraction of the muscle fibers contacted by that motor neuron
114
What neurons are efferent and the only kind of neurons to synapse on skeletal muscle?
motor neurons
115
What NT is used by motor neurons?
ACh
116
What is a motor neuron + all fibers contacted by it?
motor unit
117
fine motor skills require (larger/smaller) motor units
smaller
118
Extrafusal fibers are innervated by what types of motor neurons? What do the extrafusal fibers do?
alpha and beta MNs generate muscle force
119
What do intrafusal fibers do and what type of MNs innervate them?
modulate sensitivity, forming part of the muscle spindle gamma and beta MNs
120
What four things comprise the muscle spindle?
intrafusal muscle fibers primary sensory afferent (group Ia) secondary sensory afferent (group II) efferent neurons from beta or gamma MNs
121
The muscle spindle recognizes stretch when .... receptors are activated in afferent nerve terminals called... This will .... the afferent nerve.
mechanoreceptors sensory transduction zone depolarize
122
group Ia afferents (Aalpha) are the fastest AP conducting axons innervating the middle section of the spindle and signal...
both transient stretch and muscle length
123
group II (Abeta) afferents are moderately fast and signal...
only muscle length
124
What is the primary function of intrafusal fiber contraction?
maintain spindle sensitivity during extrafusal muscle contraction
125
What prevents there from being slack in a muscle spindle?
co-contraction of extrafusal and intrafusal fibers
126
What comprises the Golgi Tendon apparatus?
afferent fibers intertwined with collagen fibers of the tendon
127
How does the Golgi tendon signal muscle force?
collagen fibers "squeeze" afferent fibers when contraction is occurring, thus increasing force and activating mechanoreceptors.
128
What type of afferent fibers do Golgi Tendon apparatus have? How are they working here?
afferent fibers are group Ib - fast AP receptor potential is passively propagated to spike generating zone where APs initiate if receptor potential is greater than threshold.
129
Which type of muscle afferent is activated by the tendon tap?
group Ia
130
A load is applied to a muscle, but the muscle does not contract. Which receptor type will be primarily activated?
muscle spindles
131
A load is applied to a muscle, and the muscle contracts, but the intrafusal fibers do not contract. Which receptor type will be primarily activated?
Golgi tendon organs
132
A fundamental property of MNs is that they...
always have some basal AP activity
133
A myotactic unit includes:
all extensor and flexor muscles around a joint
134
For reciprocal motor control, an afferent that induces contraction of the muscle in which it resides will also induce...
relaxation in the antagonistic muscles in the myotactic unit
135
The stretch reflex is also known as the ... reflex. How is this reflex initiated?
myotactic reflex initiated by activation of muscle spindle Ia afferents
136
The inverse myotactic reflex is initiated by... What happens with this reflex?
activation of Ib afferents from Golgi tendon resident and synergistic muscles relax while antagonist muscle contracts
137
The Ia afferents from muscle spindles make direct excitatory contacts onto motor neurons that innervate
both the resident and synergistic muscles
138
To remove the limb from danger, the withdrawal reflex activates...
flexor muscle of the injured limb
139
The H-reflex used the circuitry of...
stretch reflex
140
What type of pain fibers participate in the crossed extensor reflex?
Adelta pain fibers
141
What results from the hyperactivity of the motor neurons in a muscle?
cramping
142
What is the mechanism behind treating muscle cramps?
a strong force applied activates Golgi tendon and inverse myotactic reflex to inhibit activity of the motor neurons causing cramps
143
What are inhibitory interneurons that are activated by MNs to inhibit the same motor neurons? What would this be called?
Renshaw cells feedback inhibition
144
What NT do MNs use to activate Renshaw cells?
ACh
145
Based on peripheral motor control, increased activity of gamma MNs without a change in muscle length will...
contract the muscle innervated by the gamma MNs
146
What NT do Renshaw cells use to inhibit MNs?
glycine
147
Tetanus toxin produces its clinical effects by...
preventing glycine release, ultimately decreasing Renshaw cells ability to inhibit MNs and it causes hyperactivity of MNs
148
What fiber type carries 'fast' pain, sharp, stabbing, through the dorsal horn, specifically lamina I and V
A delta
149
What fibers carry slow pain, burning or aching, through the dorsal horn? What lamina do they go through for their first synapse?
C-fibers
lamina I and II
150
Pain fibers, whether A delta or C-fibers, will cross midline and ascend in what tract?
spinothalamic
151
In short term sensitization of pain, PKA and PKC will be activated by what? What do PKA and PKC do then?
activated by Ca2+, PG, or bradykinin
PKA and PKC will phosphorylate channels like TRPV, MA, Nav, and Kv
152
Activation of what kind of touch receptors can inhibit activity of secondary nociceptors to decrease pain signals using glutamate?
Merkel cell touch receptors
153
'Wind up' is a spinal mechanism of pain sensitization that is from...
increased secondary nociceptor activation induced by repeated or continuous primary nociceptor activity
154
How can wind up be reversed?
when primary nociceptor activity returns to normal or with drugs
155
What happens if a primary nociceptor remains elevated in sensitizing pain?
increased Calcium in secondary nociceptor leads to kinase activation, leading to long term potentiation of noc. synapses
156
How does kinase mediated sensitization of pain work?
calcium activation of PKC leads to phosphorylation of AMPA and NMDA receptors leading to increased activity and increased response of secondary nociceptors to glutamate
157
How do microglia come in to play with injured neurons? What do they do?
injured neurons release cytokines and ATP that attract and activate microglia in DH
microglia will release BDNF
158
What does BDNF do in increasing pain sensitization?
exacerbates secondary nociceptors by inhibiting GABAa mediated inhibition -- hyperalgesia
continued release induces axonal sprouting, creating a low threshold for MA receptors and does some direct rewiring to secondary nociceptors - allodynia
159
What receptors use A beta fibers?
Merkel cell touch receptors
160
What are the origins of a descending pain pathway that modulates pain signals?
Anterior cingulate cortex and HT
161
From the ACC and the HT, how does the rest of the descending pain pathway go?
both go down to synapse in PAG and then continue down to the RVM (rostral ventromedial medulla).
RVM sends its axon to the dorsal horn of the spinal cord
162
What is the pain enhancement pathway?
amygdala to PAG to RVM to activate 'on cells' in RVM
this will increase activity in response to noxious stimuli - hyperalgesia
163
What is the pain inhibition pathway?
HT and ACC to PAG to activate 'off-cells' in RVM
this increases activity of inhibition of pain transmission in the dorsal horn
164
How are off-cells of the RVM activated?
endogenous opioid NT and then off-cells release endogenous opioid NT onto primary nociceptor afferents and secondary nociceptors to inhibit pain in dorsal horn
165
What is the target for all opioid analgesic drugs?
mu (MOR)
166
How does MOR work?
* pre-synaptic - inhibits Cav to inhibit NT release, inhibiting GABA, to release off-cells from tonic inhibition
* post-synaptically - activation of GIRK (inhibits on-cells)
167
What are two endogenous agents that are endocannabinoids? Which one is in greater concentration in the body?
anandamide
2-AG (greater concentration)
168
endocannabinoids are synthesized in neurons and immune cells for what purpose?
negative FB systems for inflammation and pain
169
What are the cannabinoid receptors activated by?
CB1 - both anandamide and 2-AG
CB2 - only 2-AG
170
Which cannabinoid receptor is expressed by periph and central neurons and immune cells like macrophages and microglia?
CB2
171
Which cannabinoid receptor is probably a better target for analgesic effects?
CB2
172
Which receptor is responsible for the psychobehavioral effects of THC?
CB1
173
Where are CB receptors located?
pre-synaptic side of primary nociceptors and cell bodies of secondary nociceptors with MOR and alpha2-adrenergic receptors
174
How do CB receptors work pre and post synaptically?
* pre-synaptically - GPCR \> inhibits Ca \> inhibits NT release (glutamate)
* post-synaptically - GIRK\> hyperpolarizes membrane potential of secondary nociceptor and inhibits AP
175
Activation of CB receptors and MOR will inhibit generation of pain by blocking what receptor pathways?
TRPV1
ASIC
TRPA1
176
What will block the placebo effect?
blocking MOR with naloxone
177
secondary nociceptors have their cell bodies in the
dorsal horn of spinal cord
178
What NT is released by secondary nociceptors to produce excitatory post-synaptic potentionals in tertiary nociceptors?
glutamate
179
A clinically important ion channel subunit is...
Nav Beta subunit
180
Silent nociceptors are termed silent because they...
are not activated by noxious stimuli, but still produce pain
181
Which channel type is activated during both nociceptive and inflammatory pain?
ASIC channels
182
In neuropathic pain, the levels of which ion channel type or subunit type is reduced to increase nociceptor activity?
Kv channels
183
Increased ion channel activity in peripheral neuropathic pain results from changes in
gene transcription
184
Sunburn produces allodynia by activation of
Protein Kinase A
185
A noxious stimulus that produces the same level of pain both before and after a sunburn is an example of
nociceptive pain
186
In gate-control of pain, which NT is released by Abeta fibers to cause the inhibition of secondary nociceptors?
glutamate
187
What ion channel provides calcium needed to produce Windup in secondary nociceptors?
NMDA receptor/channels
188
The primary activator of kinases to induce kinase-based sensitization is...
calcium
189
Which NT activates microglia to release BDNF?
ATP
190
What induces the block of GABAa receptor-induced inhibition of secondary nociceptors to generate central sensitization?
BDNF
191
Irreversible allodynia results from...
axonal-sprouting of non-nociceptors
192
The on-cells of the RVM are directly activated by excitatory input from neurons located in the...
PAG
193
The NT used to activate on-cells is...
glutamate
194
The mechanism that activates 'off-cells' involves disinhibition. The NT that induces disinhibition is/are...
opioid peptides
195
Morphine blocks pain signaling in the dorsal horn by...
hyperpolarizing the membrane potential of secondary nociceptors
196
Disinhibition of Off-cells is achieved by the...
inhibition of presynaptic calcium channels to block the release of GABA
197
THC is an agonist of...
CB1
198
Analgesia induced from activation of CB1 by anandamide results from...
inhibition of GABA release in RVM
199
We know that placebos activate endogenous analgesic pathways because ...
blocking MOR receptors with naloxone inhibits the placebo effect
200
Central hyperalgesia can be caused by activation of...
on-cells in the RVM
