TALBOT Q's [Membrane Biophysics & Resting Membrane Potentials, AP, Synaptic Transmissions, Actin Filaments, Muscle Contraction, The Neuromuscular Junction, Excitable Cells, Channelopathies] Flashcards
what stains actin?
rhodamine phalloidin
what stains tubulin?
anti-tubulin & fluorescein secondary antibody
what stains DNA/nucleus?
dapi
what’s the protein of actin filaments?
actin
what’s the protein of microtubules?
tubulins
what’s unpolymerized form of actin filament?
globular, monomer (G actin)
what’s unpolymerized form of MT?
heterodimer (1alpha +1beta)
what’s the bound nucleotide in actin filaments?
ATP
what’s the bound nucleotide in MT?
GTP
what’s the form of polymer in actin filaments?
2-stranded helix
what’s the form of polymer in MT?
hollow tube, 13 protofilaments
do actin filaments have dynamic instability?
yes
do MTs have dynamic instability?
yes
are actin filaments structurally polar?
yes
are Mts structurally polar?
yes
what’s the growing end of actin filament?
+ end
what’s the growing end of MT?
+ end
what’s the shrinking end of actin filament?
+ end
what’s the shrinking end of MT?
+ end
what are the roles of actin filaments?
- mircrovilli
- contractile bundles in cytoplasm
- form leading edge projections in crawling cells
- form the contractile ring in cell division
which end of actin filament do G-actin monomers bound to ATP add to?
+ end
which end of actin filament do G-acin monomers bound to ADP come off of?
- end
profilin
actin binidn protein that binds to actin monomers and facilitates exchange for ADP for ATP
treadmilling
refers to the fact that any given G-actin appears to “move along a treadmill” in that it adds on to the + end and falls off from the - end
TRUE or FALSE. “actin filament can grow or shrink at either end in vivo. however, they preferentially grow at their + end and shrink at their - end
True
ATP cap
as long as it is on the actin filament, the end in which it is located is where the actin filament grows
NOTE: if it comes off, ADP may be exposed, allowing possible shrinking at that end
severing proteins (aka. gelsolins)
they cut an actin in the middle, exposing ADP-actin on the plus end of the new fragment as well as on the new minus end; thus they promote rapid depolymerization and convert the gel-like structures into a more liquid solution
what is an example of cross-linking protein?
filamin
what are some examples of bundling protein?
fimbrin, villain, alpha-actin
what is an example of motor protein?
mysosin
what are some examples of capping (end-blocking) proteins?
capZ, tropomodulin
what is an example of side-binding/stabilizing proteins?
tropomyosin
what are some examples of nucleating proteins?
ARP 2/3, profilin
what do you call the filament growing out of ARP 2/3?
daughter filament
[difficult-long answer] what are the steps of cell crawling?
1) nucleating proteins promote pushing out actin filaments towards leading edge structures
2) bundling proteins in filopodia help form exploratory fibers
3) integrins form new adhesion point; severing proteins promote depolymerization of actin filaments
4) myosin’s walk along actin filaments, pulling rear of cell towards new adhesion point
motor domain of myosin
acts with actin and hydrolyzes ATP
what are the 3 distinct, fibrous components of the cytoskeleton?
intermediate filaments, MT, and actin
what is the similarity among the 3 distinct, fibrous components of the cytoskeleton?
they each is made of 2-13 protofilaments arranged in parallel to each other and held together by non-covalent bonds
what is the difference among the intermediate filament, MT and actin?
they each is unique in the type of protein subunits used to form each structure and in their individual roles in the cell
what are the similarities between actin and tubulin?
- bind and hydrolyze a nucleotide triphosphate and its relative form influences the affinity of the protein subunit for other subunits
- exhibit dynamic instability
- structurally polar, with functionally distinct ends
- the plus end preferentially grows whereas the mini send preferentially shrinks
what is the intracellular Na+ concentration?
15 mM
what is the interstitial Na+ concentration?
145 mM
what is the intracellular K+ concentration?
120 mM
what is the interstitial K+ concentration?
4.5 mM
what its the interstitial Ca2+ concentration?
1.2 mM
what is the intracellular Cl- concentration?
20 mM
what its the interstitial Cl- concentration?
116 mM
synaptic transmission is predominantly _____ (via NTs) but also can be _____ (via gap junctions).
chemical; electrical
in neurons that interact via _____ synapses, the pre-synaptic AP induces the secretion of NT, leading to a change in _____ in the postsynaptic cell.
chemical; Vm
in neurons that are connected by _____ synapses, the signal moves through gap junctions directly from the pre-synaptic cell to the post synaptic cell.
electrical
electrically coupled cells
cells that are connected by gap junctions
where can you find electrically coupled cells?
brain, cardiac muscle, and some smooth muscle
T/F in electrical transmission, there is some loss of voltage between the pre- and post-synaptic cell.
TRUE
T/F electrical synapses are almost always excitatory.
TRUE
what is responsible for the loss of voltage between the pre- and post-synaptic cell?
passive spread of a change in membrane potential
between electrical and chemical synapses, which one is only unidirectional?
chemical synapse
there are 9 steps in a chemical synapse. name all the 9 steps
1) NT synthesized and stored in vesicles in presynaptic cell
2) AP depolarizes nerve terminus
3) depolarization opens voltage-gated Ca2+ channels
4) Ca flows from ECF into cell
5) Ca acts as 2nd messenger, inducing vesicles to fuse with plasma membrane
6) NT released into synaptic cleft
7) NT binds to receptors on post-synaptic cell
8) this alters gating of ion channels in the post-synaptic cell
9) PSP (post synaptic potential )develops across post-synaptic cell dendritic membrane
SNARE proteins
proteins that allow the vesicle to recognize, dock and fuse to the plasma membrane; found in both vesicular membrane and palsmamembrane
which two synaptic toxins inhibit NT secretion?
botulism toxin
&
tetanus toxin
which synaptic toxin induces a massive non-specific release of NT?
alpha-latrotoxin
the vesicle contains a _____ and the target membrane contains a _____ and the 2 must interact to allow the vesicle to ultimately fuse and release its contents.
nSNARE; tSNARE
_____ allows the interaction bw the vSNARE and the tSNARE to occur, leading to secretion of NT.
calcium
how do botulism toxin and tetanus toxin inhibit NT secretion?
they are proteases (they cleave the SNARE proteins)
which synaptic toxin does black widow spider venom contain?
alpha-latrotoxin
how does alpha-latrotoxin induce a massive non-specific release of NT?
by by-passing the calcium regulation of NT secretion
what do you call complementary proteins found on both the vesicular and target membrane?
SNAREs
which type of SNARE is synaptobrevin?
vSNARE
which type of SNARE is SNAP-25 and syntaxin?
tSNARE
other than vSNARE, what is the other vesicular protein?
synaptotagmin
what does synaptotagmin bind?
calcium
other than tSNAREs, what is the other pre-synaptic plasma membrane protein?
neurexin
what are the 4 steps of docking and fusion of vesicles?
1) vesicle docks
2) SNARE complexes form, pull membranes together
3) entering Ca binds synaptotagmin
4) Ca-bound synaptotagmin catalyzes membrane fusion
what are the 3 major categories of classic NTs?
acetylcholine
amino acid
monoamines
name 3 aa NTs
GABA
glycine
glutamate
how are monoamines synthesized?
by replacing -COOH in aa with another functional group
name the monoamines (2)
catecholamines
indolamines
name the subcategories of catecholamines (3)
norepinephrine
epinephrine
doapmine
name the indolamines (2)
seretonin
histamine
which aa are indolamines formed from?
tryptophan
the subcategory of catecholamines are all modified _____ aa and are closely related to each other
tyrosine
what are the 3 characteristics of classic NTs?
1) small, clear storage vesicles
2) recycled
3) most are synthesized in nerve terminus
T/F non-classic NTs such as peptides are recycled
FALSE. non-classic NTs such as peptides are NOT recycled.
where are non-classic NTs synthesized?
in cell body
4 characteristics of peptide NTs
1) much larger variety
2) may be co-localized to the same nerve terminal as classic NTs
3) most are synthesized in cell body, usually as prohormones
3) most are enzymatically inactivated in the synapse
_____, _____ _____ vesicles often contain “classic” NTs
small, clear round vesicles
_____, _____ vesicles typically contain peptide NTs or, in some cases, _____
large, dense-core; biogenic amines
3 main mechanisms to eliminate NT from cleft
1) reuptake of NT into axon terminus or transport into neighboring glial cell
2) inactivate NT using enzymes present with in synaptic cleft
3) allow NT to diffuse from cleft into surrounding ECF or blood stream
SSRI’s
selective serotonin reuptake inhibitors; antidepressive
Glutamate synthesis and cycling between neurons and glia: The action of glutamate released into the synaptic cleft is terminated by uptake into surrounding glial cells (and neurons) via _____. Within glial cells, glutamate is converted to _____ by _____ and released by glial cells by a different transporter. _____ is taken up into nerve terminals via _____ and converted back to glutamate by _____. Glutamate is then loaded into synaptic vesicles via _____ to complete the cycle.
excitatory amino acid transporters (EAATs)
glutamine
glutamine synthetase
glutamine
SAT2 transporters
glutaminase
vesicular glutamine transporters
acetyl choline esterase (AChE)
cleaves ACh back into choline and acetate
ACh binds to one of several types of _____ receptors on the post-synaptic membrane
cholinergic
AChE inhibitors include _____ (a nerve gas) and many _____
sarin; many organophosphate pesticides
fast chemical synapses contain _____ receptors (_____ channels)
ionotropic; ligand-gated
slow chemical synapses contain _____ receptors (_____ receptors)
metabotropic; G-protein coupled
within fast chemical synapses, there are 2 subcategories based on how quickly a PSP develops in the postsynaptic cell. the speed with which the response is induced is due to differences in the __________.
type of receptor found in the dendritic membrane
how fast are the fast chemical synapses?
~1 msec
how slow are the slow chemical synapses?
secs-mins
in the slow chemical synapses, receptor _____ leads to a change in membrane potential in post-synaptic cell
indirectly
bw fast and slow chemical synapses, which one allows for amplification of the signal, leading to a larger response?
slow chemical synapse
ECF [K+]
4 mM
T/F ions can passively move up their concentration gradient if it brings the membrane potential closer to that ions equilibrium potential
TRUE
the membrane potential of a cell is -20mV, E of Cl- is -45 mV. the net flux of Cl- will be:
inward directed
the axonal membrane domain is non-conducting with regards to Na+ when the voltage-gated Na+ channel is
both closed and inactivated
which vesicular membrane-associated protein is involved in vesicular fusion to the axon terminal membrane?
synaptobrevin
the end-plate potential is the result of which of the following ionic events occurring at the nicotinic AchR?
influx of Na+ and efflux of K+
function of ARP 2/3
nucleation
function of myosin
motor protein
function of CapZ
plus end cap
function of gelsolin
severing
during the cross bridge cycle in a sarcomere, when does the “power stroke” of the myosin head occur?
during the rigor phase
the depolarization phase of an AP is carried by Ca2+ in which cells?
cardiac pacemaker cells and some smooth muscle cells
excitation-contraction coupling refers to:
how a muscle membrane AP leads to an increase in cytoplasmic [Ca2+]
malignant hypothermia can occur when _____ is mutated
RyR1 of skeletal muscle
according to the chemiosmotic hypothesis, which of the following contributes to the proton-motive force across the inner mitochondrial membrane (IMM)?
- the proton concentration gradient across the IMM
- the electrical potential gradient across the IMM
- the difference in oxygen concentration across the IMM
which ionotropic receptor? heteromeric, 5 subunits; number of different subunits varies between muscles and neuronal types; permeable to Na and K
nAChR
most serotonin receptors are G-protein coupled (metabotropic) receptors, but the _____ type is an ionotropic receptor food mostly in CNS; clinical significance as antagonists acts as anti emetics (anti-nausea), anxiolytics (anti-anxiety) and antipsychotics; permeable to Na and K
5-HT3R
which rionotropic eceptor? fx primarily in synaptic inhibition, selective for Cl-
GABA-A receptors
which ionotropic receptor? major inhibitory NT in spinal cord and brain; selective for Cl-
glycine receptor
which ionotropic receptor? several types, widespread in CNSD, primarily excitatory; receptor subtypes named for the agonists that stimulate them
glutamate receptors
name the 5 ionotropic receptors discussed in class
nicotinic AChR 5-HT3R GABA-A receptor glycine receptor glutamate receptor
name the 5 metabotropic/GPCR receptors found on the post-synaptic membrane
- muscarinic AChR
- g-aminobutyric acid (GABA) receptor
- metabotropic glutamate -receptors (mGluR)
- a and b adrenergic receptors
- dopamine receptor (DaR)
most of the _____ are localized to the corpus striatum and take part in coordinating motor fx
dopamine receptor (DaR)
T/R a and b adrenergic receptors can be activated by either Nor or Epi (with vary affinities). these receptors are found in the brain as well as throughout the body
TRUE
_____ are one of the more unique GPCR family members and have only minimal sequence homology
metabotropic glutamate receptors (mGluR)
_____ are found in the brain, leading to either excitation or inhibition, depending on the receptor subtype activated
muscarinic acetylcholine receptor
_____ receptors indirectly activate their effector protein
G-protein coupled receptors
metabotropic receptors indirectly lead to the opening of _____
ion channels
what are the 2 ways in which a NT binding got a GPCR/metabotropic receptor can lead to the opening of ion channels
1) the activated G-protein can directly bind and change the gating of an ion channel
2) the activated G-protein can activate an enzyme that leads to the production of 2nd messenger in the cell. the 2nd messenger then binds to and opens specific ion channels
cardiac pacemaker cells are innervated by the _____ nerve of the (sympathetic/parasympathetic) nervous system; _____ is the NT.
vagus; parasympathetic; ACh
cardiac pacemaker cells are innervated by the vagus nerve of the parasympathetic nervous system; ACh is the NT. ACh binds to the (nicotinic/muscarinic) AChR GPCR and _____ the G-protein; here the G_____ subunit is the active unit.
muscarinic; activates; beta-gama
cardiac pacemaker cells are innervated by the vagus nerve of the parasympathetic nervous system; ACh is the NT. ACh binds to the muscarinic AChR GPCR and activates the G-protein; here the Gbeta-gamma subunit is the active unit. Gbeta-gama binds to a _____ channel in the _____ membrane, opening it and allowing _____ to flow (in/out) of the cell
K+; plasma; K+; out
K+ (influx/efflux) (hyper/hypo)polarizes the membrane of the pacemaker cells, which leads to a (increase/decrease) in the heart rate
efflux; hyper; decrease
T/F an example of a postsynaptic cell with a metabotropic receptor where the G-protein directly affects the gating of the ion channel can be seen in cardiac pacemaker cells.
TRUE
binding of NT to receptors in the postsynaptic membrane leads to changes in Vm –> _____ potentials
graded
what do you call ion flow across a membrane?
current
_____ influx always produces an EPSP (excitatory postsynpatic potentials)
Na+
_____ efflux always produces an IPSP (inhibitory postsynaptic potentials)
K+
_____ flux (in or out) typically produces an IPSP (inhibitory postsynaptic potentials)
Cl-
T/F the somatodendritic domain cannot produce APs, but an EPSP can increase the likelihood of developing an AP at the axon hillock
TRUE
T/F the somatodendritic domain cannot produce APs, but an EPSP can decrease the chance of an Ap forming at the axon hillock
TRUE
how do you increase the chance of developing an AP? (3)
1) produce EPSP closer to axon hillock
2) decrease threshold voltage
3) summation=larger EPSP
you often see (excitatory/inhibitory) synapses closer to axon hillock
inhibitory
spatial summation of PSP
several different presynaptic neurons firing (at same time) at different synapses
temporal summation of PSP
- same or nearby presynaptic neuron firing multiple times in close succession
- stimulation may occur if multiple EPSPs occur within a short duration
summation can occur over both _____ and _____
time, space
_____ the time constant, the longer the Vm stays above rest from each incoming PSP in temporal summation. thus the more likely summation can occur
greater
spatial summation of PSP: _____ the length constant, the further the change in Vm will travel before it decays back to rest, thus increasing the likelihood that it can interact, sum, with a PSP received at a different part of the membrane.
greater
membrane time constant represents the time it take the membrane to reach _____% of the final voltage
63%
membrane time constants of different neurons typically range from _____ to _____ ms
1-20ms
what does membrane time constant affect?
how long it takes before membrane potential returns to its resting value
[LIKELY HIGH YIELD] T/F the longer the time constant, the longer the membrane potential will take to return to its resting potential (implications for integration of multiple incoming signals)
TRUE
cholinergic receptor
binds to ACh; the 2 main subtypes of cholinergic receptors include nicotinic cholinergic receptors and muscarinic cholinergic receptors
adrenergic receptor
binds the 2 main catecholamines (norepinephrine and epinephrine); named after the adrenal gland (which secretes epinephrine). many different subtypes within 2 main classes (alpha and beta)
serotonergic receptor
binds serotonin
histaminergic receptor
binds histamine
agonist
activator; a chemical that is usually a structural analog of the natural ligand such that when it bind sot the binding site on the receptor, it induces the normal response
GPCR
G-protein coupled receptor
ICR
ion channel receptor = ligand-gated ion channel = ionotropic receptor
what do you call muscle plasma membrane?
sarcolemma
[LIKELY HIGH YIELD] what does sarcolemma contain?
- depressions with junctional folds on the post-synaptic side of the motor end plate
- transverse or T-tubules (invaginations)
- voltage-gated Na+ and K+ channels
what are the 2 membrane domains in the SR?
1) longitudinal elements
2) terminal cisterane
what is the calcium storage site in skeletal muscle?
SR (sarcoplasmic reticulum)
neuromuscular junction
a specialized chemicla synpase bw the nerve terminus of a motor neurons and a skeletal muscle
[LIKELY HIGH YIELD] T/F each skeletal muscle fiber is only innervated by a single neuron, but a motor neuron can synapse on multiple muscle fibers.
TRUE!
[LIKELY HIGH YIELD] what is a motor unit?
a single motor neuron and all the muscle fibers it innervates
the _____ muscle fibers in a motor unit, the finer the control
fewer
the greater the number of fibers in a motor unit, the _____ the force of contraction can be
stronger
the neuromuscular junction consists of: _____, _____, and _____
1) presynaptic nerve terminus
2) synaptic cleft
3) post-synpatic motor end plate
what does the presynaptic nerve terminus of the neuromuscular junction contain?
vesicles filled with ACh
how big is the synaptic cleft of the neuromuscular junction?
50 nm
what does the synaptic cleft of the neuromuscular junction contain?
ACh esterase on the cleft side of the post-synpatic membrane & proteins associated with an extracellular matrix
T/F the post-synaptic motor end plate of the neuromuscular junction is a skeletal muscle cell membrane.
TRUE
what does the post-synaptic motor end plate of the neuromuscular junction contain?
terminal folds
each vesicle in a neuromuscular junction contains _____ ACh molecules
1,000
1 vesicle in a neuromuscular junction = 1 _____
quanta
each vesicle in a neuromuscular junction is _____ diameter
50 nm
in the postsynaptic membrane of the neuromuscular junction, clusters of nicotinic ACh receptors are in the _____
junctional folds
the size of the synaptic cleft bw nerve and muscle cells
50-100 nm
how long does it take for ACh to diffuse in the synaptic cleft bw nerve and muscle cells?
0.5 ms
presynaptic clusters of ACh containing vesicles, arranged in orderly manner right _____ active zone (primary region of vesicular fusion)
above
AChR clustered just _____ active zone; mosat receptors _____ top of junctional folds
below; near
T/F various glycoproteins form synaptic basal lamina that help adhere presynaptic nerve terminus to junctional folds.
TRUE
calcium channels are concentrated at the NMJ in regions of the _____ nerve terminal opposite clusters of AChRs on the _____ membrane
presynaptic; postsynpatic
each polypeptide subunit shares significant homology and spans the membrane 4x with the _____ exposed to the _____ of the synaptic cleft
N-temrinus; extracellular fluid
nicotinic AChR is a mixed cation channel with permeability to both Na and K but the driving force for _____ entry is greater, leading to a net _____
Na; depolarization
[LIKELY HIGH YEILD] whereas the skeletal muscle nicotinic receptor is composed of _____ different subunits, the neuronal nicotinic AChR is composed of only ____ subunit types
4; 2
[LIKELY HIGH YIELD] the subunits of the NMJ nAChR contain recognition sites for agonists such as..
nicotine
[LIKELY HIGH YIELD] the subunits of the NMJ nAChR contain recognition sites for reversible antagonists such as..
curare
[LIKELY HIGH YIELD] the subunits of the NMJ nAChR contain recognition sites for alpha-toxins such as..
cobra alpha-toxin & alpha-bungarotoxin
cobra alpha toxin and alpha-bungarotoxin are both from _____ venoms
snake
neostigmine
a reversible ACh esterase inhibitor
in the following findings in a clinical case, “muscle response with reposted direct stimulation of the muscle is normal,” what is implied by direct stimulation of the muscle?
an external electrical stimulus such as shock that non-specifically depolarizes the membrane potential
end plate potentials: when the AChR ion channel on post-synaptic membrane opens, both Na and K flow (up/down) their electrochemical gradient
down
[LIKELY HIGH YIELD] at resting potential, net driving force for _____ is much greater than _____, when ACh triggers opening of these channels more _____ moves inwards than _____ outwards, depolarizing the endplate. this potential change is called _____.
Na K Na K end plate potential (EPP)
T/F EPP (end plate potential) is an AP
FALSE. EPP is not an action potential
T/F EPP (end plate potential) is simply depolarization of specialized motor end plate, analogous to an EPSP in a postsynaptic neuron
TRUE
[LIKELY HIGH YIELD[]each EPP produces a _____ that _____ the production of an _____ along the sarcolemma
suprathreshold depolarization; triggers; AP
the resting Vm of most skeletal muscle is close to _____mV
-90mV
in both adult and fetal AChR, the _____ is 0 mV. this is because the AChR ion channel is equally permeable to both Na and K, and since they have similar (but opposite) chemical gradients, in the absence of an _____, there will be no net flux (current = 0)
reverse potential; electrical gradient
the number of ACh molecules in each vesicle is called a _____
quantum
_____ specifically refers to non-stimulated events due to the random fusing of vesicles to the active zone of the nerve terminus
miniature EPPs
myasthenia gravis
an autoimmune disease in which patients develop antibodies against nicotinic ACh receptors
myasthenia gravis is an autoimmune disease in which patients develop antibodies against nicotinic ACh receptors. thus, the amplitudes of MEPPs and EPPs are reduced (why?) and the muscle membrane may not be depolarized sufficiently to fire an AP
since there will be less depolarization for the same ant of released ACh
how do you treat myasthenia gravis?
give an acetylcholinesterase inhibitor to prolong and increase the AP of ACh at the available receptors and to restore the muscle AP
what are the symptoms of myasthenia gravis?
- eye muscle weakness
- eyelid drooping
- blurry/double vision
- unstable gait
- change in facial expression
- difficulty in swallowing
- shortness of breath
- impaired speech
- weakness in the arms, hands, fingers, legs and neck
curare
-non-depolarizing muscle relaxant/paralytic
T/F curare is an anesthetic
FALSE. curare is a relaxant/paralytic
what does curare block?
nicotinic receptors
what do you need to be careful about curare?
patients may feel pain but cannot show it
what does neostigmine block?
cholinesterases
neostigmine is a component of _____ and _____
nerve gases & insecticides
what results from defects in the ClC-1 Cl- channel?
myotonia congenita (myopathy)
in skeletal muscle, why isn’t there an “after hyper polarization” after an AP?
because the resting Vm in skeletal muscle is closer to Ek
[LIKELY HIGH YIELD] what are the differences bw skeletal muscle and neuronal membrane potentials?
- skeletal muscle maintains a more negative resting membrane potential usually closer to -90mV
- the T-tubule membranes contains a chloride channel (ClC-1) that contributes to the resting Vm
the more negative Vm of the skeletal muscle is due to: (2)
1) increased K gradient
2) increased Cl- gradient and Cl- permeability
[LIEKLY HIGH YIELD] excitation-contraction (EC) coupling
the muscle membrane AP indirectly induces the release of calcium from the SR, leading to contraction
excitable cells
- cells that are capable of developing APs across their plasma membranes
- maintain a resting Vm
- contain voltage-gated ion channels
[LIKELY HIGH YIELD] the T-tubule membranes contains a _____ that contributes to the resting Vm along the K leak channel
chloride channel (ClC-1)
what are the similarities bw skeletal muscles APs and neuronal APs? (4)
1) resting potential maintained in absence of incoming stimulus
2) voltage-gated Na channels open 1st, induce initial rapid depolarization
3) Na channels inactivate as voltage-gated K channels open (delay)
4) K channels allow depolarization of membrane potential
[LIKELY HIGH YIELD]when K channels allow depolarization of membrane potential, what happens to neuron and skeletal muscle?
neuron hyper polarize BUT skeletal muscle does not
in addition to the voltage-gated Na and K channels in the sarcolemmal T-tubules, there is also a member of the voltage-gated Ca channel family –> the _____ receptor
DHP Receptor
a triad is 1 _____ and the _____ of 2 _____ regions
T-tubule; terminal cisternae; SR
the T-tubule contains the voltage-sensitive DHP _____ channels
calcium
the SR terminal cistern contain calcium release channels known as ____ receptors
Ryanodine
depolarization of the T-tubule membrane indirectly induces _____ release: this is known as _____
calcium; excitation-contraction coupling
intercalated disks contain:
1) gap junctions
2) desmosomes
gap junctions allow direct electrical coupling of _____
myocytes
_____ conduction of APs between cells through the gap junctions
rapid
desmosomes
- cell-to-cell junctions
- allow force transfer bw cells
what are the 3 kinds of cardiac muscle cells?
autorhythmic
conducting cells
contractile cells
which of the cardiac muscle cells are pacemaker (nodal) cells?
autorhythmic
which of the cardiac muscle cells are Purkinje fibers?
conducting cells
which 2 types of cardiac muscle cells have little actin and myosin?
autorhythmic and conducting
[LIKELY HIGH YIELD] myogenic muscle cells _____ depolarize, initiating contraction when the threshold potential is reached
spontaneously
“pacemaker” refers to the fact that the time bw contractile events is set by the _____ rate of depolarization and not an external signal
intrinsic
[LIKELY HIGH YIELD] DHP receptor
L-type Ca2+ channel
Ryanodine receptor
the SR calcium release channel
tetanus
greater and prolonged contraction
what is the predominant smooth muscle type in wall of visceral organs and blood vessels?
single-unit smooth muscle
where can you find multi-unit smooth muscle?
- trachea
- iris and ciliary body of the eye
- piloerector muscles of the skin
- some blood vessels
in most cases, the depolarization phase of the smooth muscle action potentials is carried by _____ via voltage-gated _____ channels
calcium; calcium
neurogenic smooth muscle requires the binding of a _____ to a receptor to initiate the depolarization phase of the AP
NT
bw neurogenic and myogenic smooth muscles, which can spontaneously depolarize?
myogenic smooth muscle
does multi-unit smooth muscle have gap junctions?
no
does single-unit smooth muscle have gap junctions?
yes
is initiation of contraction for multi-unit smooth muscle neurogenic or myogenic?
neurogenic
is initiation of contraction for single-unit smooth muscle neurogenic or myogenic?
myogenic
does multi-unit smooth muscle have T-tubules?
no
does single-unit smooth muscle have T-tubules?
no
how much SR does multi-unit smooth muscles have?
very little
how much SR does single-unit smooth muscles have?
very little
multi-unit source of calcium for contraction
ECF/SR
single-unit source of calcium for contraction
ECF/SR
muscle AP in multi-unit smooth muscles?
no
muscle AP in single-unit smooth muscles?
yes
is multi-unit smooth muscle responsive to stretch?
no
is single-unit smooth muscle responsive to stretch?
yes
[LIKELY HIGH YIELD] how is multi-unit smooth muscle similar to skeletal muscle?
- doesn’t have gap junctions
- neurogenic initiation of contraction
- SR as source of calcium for contraction
- doesn’t respond to stretch
[LIKELY HIGH YIELD] how is multi-unit smooth muscle different from skeletal muscle?
- doesn’t have T-tubules
- very little SR
- ECF as one of the sources of calcium for contraction
- no muscle AP
[LIKELY HIGH YIELD] how is single-unit smooth muscle smilier to skeletal muscle?
- SR as source of calcium for contraction
- muscle AP
[LIEKLY HIGH YIELD] how is single-unit smooth muscle different from skeletal muscle?
- has gap junctions
- myogenic initiation of contraction
- doesn’t have T-tubules
- very little SR
- ECF as one of the sources for calcium for contraction
- responds to stretch
bw multi-unit and single-unit smooth muscles, which is more similar to skeletal muscle?
multi-unit smooth muscle
the striations in skeletal and cardiac muscles are due to…
regular arrangements of the contractile unit of muscle, the sarcomere
why isn’t smooth muscle striated?
because it lacks regularly arranged sarcomeres
[LIKELY HIGH YIELD] whats special about cardiac muscle that is different from skeletal and smooth muscles?
individual cardiac muscle cells may branch
which muscle cell is electrically coupled via gap junctions?
cardiac and some smooth
in cardiac muscle, gap junctions and _____ (which act to hold the cells together) are localized to structures called _____
desmosomes; intercalated disks
T/F some types of smooth muscles are electrically coupled via gap junctions.
TRUE
T/F only cardiac muscles cells are electrically coupled via gap junctions
FALSE
there are other cell types that contain voltage-gated ion channels, allowing the membrane to respond to depolarizations but not necessarily produce an AP. For example, _____ contain voltage-gated calcium channels that open in response to a depolarization induced by the closing of a specific type of potassium channel in their membrane
beta cells of the pancreas
[LIKELY HIGH YIELD] channelopathies
diseases caused by mutations in genes that encode ion channel subunits or regulatory proteins
ion channels are not open continuously but open and close in a _____ or _____ fashion
stochastic; random
what affects ion channel function?
1) changing the pen time
2) changing the closed time
3) changing the single channel current amplitude
4) changing the number of functional channels
ion channel function may be affected by chaining the open time, closed time, single channel current amplitude, or number of functional channels. changes in any of these can change the relative _____ of an ion.
conductance
defects that act to produce channel protein and traffic it to/from the membrane impact _____
the number of open functional channels available in a membrane
defects that impact ion conduction, gating and inactivation typically are impacting the _____ or _____
open probability OR current amplitude
[LIKELY HIGH YIELD] general characteristics of channelopathies
- although mutation is continuous, the disease may be episodic or progressive
- abnormalities in same channel may present with different disease states
- lesions in different channels may lead to same disease
[LIKELY HIGH YIELD] is periodic paralysis (channelopathy) episodic or progressive?
episodic
[LIKELY HIGH YIELD] is spinocerebellar ataxia episodic or progressive?
progressive
[LIKELY HIGH YIELD] which 2 channelopathies present with different disease states even though they are results of abnormalities in the same channel (SCN4A)?
hyperkalemic periodic paralysis & paramyotonia congenita
[LIKELY HIGH YIELD] which 2 channelopathies present with different disease states even though they are results of abnormalities in the same channel (CACNA1A)?
episodic ataxia & familial hemiplegic migraine
[LIKELY HIGH YIELD] SCN4A is a (Na/Ca) channel
Na
[LIKELY HIGH YIELD] CACNA1A is a (Na/Ca) channel
Ca
[LIKELY HIGH YIELD] lesions in which channels lead to periodic paralysis?
SCN4A, CACNA1S, Kir2.6
[LIKELY HIGH YIELD] lesions in which channels lead to long QT syndrome?
KVLQT1, SCN5A, CACNA1A
myotonia
characterized by delayed relaxation (or maintained contraction) of muscle following a sudden forceful contraction; it is associated with repetitive AP generation, a manifestation or sarcolemmal hyperexcitability
[LIKELY HIGH YIELD] periodic paralysis
- characterized by episodic weakness or paralysis of voluntary muscles (occurring with normal neuromuscular transmission and in the absence of motor neuron disease)
- it represents a transient state of hypo excitability or unexcitability in which APs cannot be generated or propagated
what are the 2 symptoms that are characteristic of muscle membrane (sarcolemma) NavCh dysfunction?
myotonia and periodic paralysis
T/F malignant hyperthermia occurs more often in adults than in children.
FALSE. malignant hyperthermia occurs more often in children than in adults because by the time the pts become adults, they would have ben treated.
