Exam 2 Flashcards
(125 cards)
1
Q
how do we test the proposed functions of domains of channel proteins?
A
sequence homologies– determine which portions of primary sequences of ion channels are same/very similar (we look at the same channel from several different species, and what is conserved must be important)
2
Q
sequence homologies in the ACh gated channel
A
ACh receptor portion of the channel is highly conserved
3
Q
sequence homologies in Vg channels
A
they all have a membrane spanning region with charged amino acids at each third position; the voltage sensor is found only in voltage gated channels
4
Q
structure of voltage gated channels
A
six transmembrane motifs, voltage sensor on S4, pore between S5 and S6; it takes four motifs to make a functional channel
5
Q
what amino acid is highly common in voltage sensors
A
arginine
6
Q
each ion has a different
A
radius, number of water molecules, and diameter of first hydration shield
7
Q
carbonyls
A
replace shell of hydration in K+ but not Na+ in the K+ channel
8
Q
procedure to transplant neurotransmitter receptors from brain to oocytes
A
injecting cell membranes or brain mrna
homogenize brain sample, centrifuge, collect and inject vesicles into oocyte
you can also homogenize then separate polyA+ RNA, inject it and wait 6 days to record
9
Q
advantages of xenopus oocytes for studying ion channels
A
big cells so easy to do electrophysiology, will express large amounts of channel of interest, can introduce exogenous channel from native sources or recombinant DNA
10
Q
patch clamp technique
A
record a small portion of the cell and current in that cell: can be cell-attached, whole-cell, or outside-out recording
11
Q
patch clamp can be used to study
A
currents through individual ion channels
12
Q
Na and K+ channels ______ by depolarization
A
are opened
13
Q
VgNA+C at depolarization
A
quickly open, inactivate, returned to closed state
14
Q
VgK+C at depolarization
A
don’t inactivate, delayed/slower opening
15
Q
alpha subunits
A
are the pore forming subunits
16
Q
K+ channels are a
A
family of voltage gated channels with greatest diversity
17
Q
function of K channels
A
regulating excitability in many tissues, in axons and somatodendritic compartments; also help set resting potential
18
Q
protein name format for voltage gated channels
A
ion, subscript family name (v for voltage), family number, position or individual number of protein
Nav1.7
19
Q
Kv2.1
A
don’t inactivate, contribute to the falling phase of the AP, called delayed rectifiers
20
Q
Kv4
A
an A type channel that rapidly inactivates, regulating AP frequency in areas like the hippocampus
21
Q
HERG channels (Kv11.1)
A
delayed current after depolarization, contribute to duration of hyperpolarization after depolarization
22
Q
Inward rectifying channels
A
more active at hyperpolarized potentials, increasing threshold for AP and including KATP to produce K+ when ATP is low
23
Q
Kca
A
protect neurons from excess depolarization when Ca2+ is high (more conductance with more Ca2=)
24
Q
2-p family
A
K+ leak channels that set resting potential
25
functions of K+ channels
resting membrane potential
mediate AP downstroke
regulate length of hyperpolarization after AP
regulate excitability in dendrites
decrease excitability during metabolic stress like high ca and low atp intracellularly
26
channelopathies
diseases caused by ion channel dysfunction, can be caused by genetic mutation or can be acquired via an autoimmune attack, can have developmental or episodic manifestations and affects many tissues,
27
episodic disorders
affect excitable tissues like brain, muscles, heart, characterized by attacks
28
causes of episodic disorders
mutations to channels or to excitability, autoimmune diseases, brain lesions/tumors
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what triggers an attack?
ion imbalance, chemical triggers, stress, etc
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seizure
abnornal/excessive excitation or synchronization of a population of neurons
31
epilepsy
spontaneous recurrent seizures unprovoked by any systemic or acute neurologic insults
32
epileptogenesis
sequence of events that converts a normal neuronal network into an epileptic network
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epilepsies
many but not all caused by channelopathies with excess Na/Ca currents or reduced K/Cl currents
caused by periodic excess excitation in brain, GOF in depolarizing, loss of function in hyperpolarizing
34
hyper and hypokalemic periodic paralysis
muscle weakness triggered by exercise or stress, causing loss of muscle tone; categorized by levels of potassium associated with attacks and caused by mutations in ion channels in skeletal muscle
(hypo: low serum K_
35
in hypokalemia, low serum K+ is accompanied by
prolonged inactivation/reduced function of VgNaCs
36
prolonged inactivation/reduced function of VgNaCs means that
muscle excitability is insufficient to complete movements
37
migraines and seizures occur after
excess excitation in the brain; GOF in depolarizing or LOF in hyperpolarizing
38
familial hemiplegic migraine
disorder characterized by headaches and weakeness on one side of the body, many known genetic causes including more activity of Cav2.1
39
GEFS
generalized epilepsy with febrile seizure, seizures accompanied by high body temp, mutations cause slowed inactivation of VgNAcs, so excess depolarization when AP is triggered
40
list some diseases caused by altered ion channels
gefs, myotonia, paralysis
41
episodic ataxia type 1
uncoordinated movement provoked by stress, startle, exercise caused by LOF mutations in K channels in cerebellum, causing inadequate repolarization
42
Nav1.7
mediator of aps in nociceptive neurons
43
congenital insensitivity to pain
lack of pain perception, characterized often by injury or loss of extremities; loss function of Nav1.7 causing less output by DRG neurons
44
paroxysmal extreme pain disorder
more activity of Nav1.7, reduced inactivation, episodes of extreme pain in jaw, eyes, rectum
45
Nav1.7 associated with
congenital insensitivity to pain and paroxysmal extreme pain disorder
46
myotonia
delayed relaxation of muscle after contraction/movement due to loss of hyperpolarizing Cl- current in muscle prolonging contraction
47
function of electrical synapses
synchronization of electrical activity of large neuron populations
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why is synchronization in electrical synapses important
important for functions requiring fast responses like reflexes and pacemakers
49
electrical vs chemical synapses
chemical involves neurotransmitter across a membrane, electrical involves direct connection via gap junctions where ions flow directly between cells
50
distance between membranes in gap junctions
wider part is 20 nm, closer part is 3.5 nm
51
connexin
a subunit of connexonm 6 connexins make a connexon in pre or post synaptic membrane, and two hemi channels come together to make one gap junction channel
52
connexin topology and structure
4 alpha helices connected by extracellular loops
53
how large are connexon pores
large enough to pass ions and small molecules, size cutoff is 500 Da for vertebrates and 1000 for invertebrates
54
do connexons have a negatively charged path
yes, in the edges of the membrane facing cytoplasm
55
function of gap junctions
rapid signalling between neurons due to coupling, so postsynaptic response is a fraction of a millisecond after presynaptic
56
gap junctions in the brain
allow for synchronous activity in hippocampus, thalamus
in hypothalamus, neurons secreting peptide hormones are connected by gap junctions, allowing for a burst of hormone
57
majority of synapses in our nervous system are
chemical synapses, which are slower but more diverse in signalling
58
characteristics of chemical synapses
- slower than electrical, diverse in signaling
- fast, local (msec, tens of nm)
- postsynaptic cell contains receptors for neurotransmitter
59
presynaptic terminals are distinguished by
synaptic vesicles
60
postsynaptic side is distinguished by
postsynaptic density
61
how long is the response delayed at the postsynaptic terminal
1 msec
62
vesicular neurotransmitter release is
quantized, meaning the vesicles empty their entire contents and discrete amounts of NT are released (as seen in mini postsynaptic potentials)
63
spontaneous miniature EPPs
occur in postsynaptic cell even without presynaptic stimulation
64
vesicles vary in appearance based on
neurotransmitter they contain
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what contributes to differential release probability?
differential positioning of vesicle types
66
vesicles close to active zone
readily releasable, high release probability, moderate Ca influx
67
vesicles far from active zone
lower release probability, larger sustained Ca influx
68
low frequency stimulation
preferential release of small-molecule nt
69
high frequency stimulation
release of both types of nt
70
vesicular NT release can be altered
to change synaptic strength
71
axo-axonic synapses
promote of prevent neurotransmitter release
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release probability
intrinsic likelihood a vesicle will fuse with plasma membrane
73
when release probability is high
presynaptic terminal releases more nt
74
low release probability
less nt is released
75
can the presynaptic release probability be altered
yes, changes synaptic strength; brief increase in release after high frequency APs (tetanus)
76
post tetanic potentiation
brief increase in release probability following high frequency short train of action potentials, partially due to higher calcium levels in cell after tetanus
77
post tetanic depression
longer term decrease in release probability following medium frequency longer train of action potentials (tetanus), usually due to depletion of NT vesicles
78
NMJ is useful for study
due to accessibility, importance in function
79
electrically excitable tissues
neurons, cardiac, skeletal
80
process of muscle contraction
muscle cell plasma membrane depolarizes, travels down T tubules, which interact with ER, causing Ca release into cytoplasm, myosin moves against actin, causing contraction
81
acetylcholine binds
nicotinic ach receptors (cation channels, so permeable to na and K)
82
sufficient depolarization triggers muscle cell
action potential, which requires Na+ channels in muscle cell membrane (sarcolemma)
83
nAch receptor is made of
5 subunits
84
one nach4 binds ___ to open
2 Ach molecules
85
the reversal potential for nAchRs is
0 mV, reflecting equal permeability to Na and K
86
reversal potential for an ion channel
membrane potential at which there is no net current, so electrochemical forces balance out
87
gaba lets in what ion
Cl-
88
reversal potential for GABA receptor
-50 to 60 mv, same as equilibrium for Cl
89
how does lower external Na affect reversal potential
shifts it to the left
90
how does higher external K+ affect reversal potential
shifts it to the right
91
what determines current amplitude?
drive/size of electrochemical gradient: closer membrane is to equilibrium potential, smaller net current
92
ion channels are not binary (T/F)
F
93
if reversal potential is more positive than threshold
excitation occurs
94
reversal potential more negative than threshold
inhibition occurs
95
IPSPs can depolarize the postsynaptic cell if
reversal potential is between resting and action potential threshold
96
synaptic contact can occur
on cell body, dendrites, or axon
97
spatial summation
synaptic potentials summed from multiple synapses across neuron
98
temporal symmation
one synapse elicits psps that are summed
99
AP frequency is shaped by
inhibitory input
100
synapses near where will have the greatest weight in summation?
axon hillock
101
threshold is lower for AP where
at hillock, enriched with NaCs, allowing distal dendritic potentials to elicit an AP
102
formal criteria for neurotransmitter
- chemical must be synthesized in neuron or otherwise present in it
- when the neuron is active, the chemical must be released and produce a response in some target
- the same response must be obtained when the chemical is experimentally placed on the target
- a mechanism must exist for removing the chemical from its site of activation after its work is done
103
what is a neurotransmitter?
molecules that
- carry messages between neurons via influence on postsynaptic membrane
- have little or no effect on membrane voltage but have a common carrying function like changing synapse structure
- communicate by sending reverse-direction messages that have an impact on the release or reuptake of transmitters (retrograde signaling)
104
nearly ubiquitous NT
glutamate (excitatory)
GABA/glycine (inhibitory)
105
neurotransmitters associated with specific neural circuits/functions
- ach
- dopamine
- norepinephrine
- serotonin
- peptide NT
- atypical NT
106
small molecule neurotransmitters
ach, amino acid neurotransmitters, amine neurotransmitters, purines
107
acetylcholine
excitatory via nicotinic ach receptors (ionotropic)
excitatory or inhibitory via muscarinic ach receptors (metabotropic)
108
amino acid NTs
glutamate, aspartate, GABA, glycine
109
glutamate
major excitatory nt of cns (ionotropic; metabotropic may be excitatory or inhibitory)
110
gaba/glycine
inhibitory cns, metabotropic gaba are inhibitory
111
amine nt
gpcr signalling (metabotropic), dopamine, norepinephrine, epinephrine, serotonin, histamine
112
small molecule nt
ATP usually copackaged with another small molecule transmitter
113
peptide hormones
also act as neurotransmitters, examples are enkephalins
114
how are nt made
cannnot cross bbb, so made locally from precursors, packaged into vesicles, signal terminated by degradation or reuptake
115
peptide nt synthesis
translation of protein in RER, precursor peptide copackaged with enzymes to make mature peptide transmitter, vesicle transported to axon terminal via active transport, after release, nt signal terminated by diffusion away from the cleft
116
proteolytic processing of pre-propeptides
pre-propeptide has signal sequence cleaved off to become a propeptide, becomes active peptides
117
neuronal signalling depends on
type of nt, neuron, brain region, receptor
118
ionotropic receptor diversity
within one receptor, subunit variants like in nAchRs, families of receptors may pass different ions, like glutamate ampa vs nmda- calcium
119
structure of gaba
pentameric cl channels
120
ampa type glutamate receptor
4 subunits
121
ioniotropic nt receptors
same endogenous ligand, different agonists, pass na, k, ca, cl, may be desensitized or voltage gated
122
ampa receptors
large current, quick desensitization
123
kainate and nmda
smaller peak current, slower desensitization
124
nmda type glutamate receptors
ligand and voltage gated so mg blocks at negative potentials, but at higher potentials mg is kicked out
125
