Smooth muscle Flashcards
how does the synaptic input to smooth muscle differ from skeletal muscle?
- neurons are part of the autonomic NS instead of somatic NS.
- the neuron makes multiple synaptic contact through varicosities.
what are varicosities
multple synaptic contacts with a smooth muscle cell that contain the presynaptic machinery for vesicular release of transmitter
is the postsynaptic membrane of smooth muscle specilalized
little specialisation
What is multi unit smooth muscle
each muscle cell gets it own synaptic unput, but there is little intercellular EC. as a result smooth muscle cells may contract independently.
what kind of smooth muscle is found in the iris and the piloerector muscle of the skin
multi unit
what kind of smooth muscle is capable of fine control
multi unit
what is unitary or single unit smooth muscle?
a group of cells that work as a syncytium because gap junctions provide electrical and chemical communication between neighboring cells.
do gap junctions in unitary smooth muscle cause chemical or eletrical communication?
both
what gives rise to the spreading of Calcium waves
Gap junction that allow ions and small molecules to diffuse between cewlls.
what kind of smooth muscle is found within the walls of viscera
unitary smooth muscle
what is visceral smooth muscle
unitary smooth muscle
The functional size of the unit depends on the strength of intercellular coupling. For example, in the bladder, extensive coupling among cells defines large functional units, which allows the cells of the muscular wall of the bladder to contract in synchrony. On the other hand, the smooth-muscle cells of blood vessels couple to form smaller, independently functioning units that are more akin to multiunit smooth muscle.
The functional size of the unit depends on the strength of intercellular coupling. For example, in the bladder, extensive coupling among cells defines large functional units, which allows the cells of the muscular wall of the bladder to contract in synchrony. On the other hand, the smooth-muscle cells of blood vessels couple to form smaller, independently functioning units that are more akin to multiunit smooth muscle.
what is different about changes to Vm changes in smooth muscle
action potentials initiate contraction in both skeletal and cardiac muscle, diverse changes in membrane potential ( V m ) can either initiate or modulate contraction in smooth-muscle cells
You see a AP that looks like those seen in skeletal muscles, what kind of smooth muscle is probabky reponsible.
unitary smooth muscle
some in multiunit
can all smooth muscle cells generate AP?
not all
What can generate a graded response in smooth muscle
circulating and local humoral factors and mechanical stimilu such as stretching the cell.
is the AP of unitary smooth muscle longer or shorter than of skeletal
a slower upstroke and longer duration (up to ~100 ms)
what reflects the depolarizing phase of smooth muscle?
opening of L-type voltage gated calcium channels.
what channels open faster cav or Nav
Nav are faster, thats why the rate of AP in smooth muscle is slower
Why is repolarisation of smooth muscle slower?
L-type Cav exhibit prolonged opening and inactivate slowly, and delayed activasion of voltage gated K channels, n many cases, Ca 2+ -activated K + channels, which depend on significant elevation of [Ca 2+ ] i .
is hyperpolarisation slow in smooth muscle
yes
where do plateau AP take place in smooth muscle?
genitourinary tract, including the ureters, bladder, and uterus.
what does plateau in AP do?
prolonged entry of Ca 2+ , thereby elevating [Ca 2+ ] i and prolonging the contraction.
why do some smooth muscle cells have Nav channels?
not appear to be necessary for generating an action potential but rather contribute to a greater rate of depolarization and thus the activation of voltage-gated Ca 2+ channels.
what are the interstitial cells of Cajal
pacemaker cells of the intestine, that control rhythmic contractions
can pacemakers hyperpolarise?
yes
what are slow waves
regular, repetitive oscillations in V m —and contractions— caused by smooth pacemakers, that occur at a frequency of several cycles per minute.
what is a hypothesis for Slow waves
some voltage-gated Ca 2+ channels—active at the resting V m —depolarize the cell enough to activate more voltage-gated Ca 2+ channels. which may well or not cause AP
What may cause spontaneous electrical activity.
Oscillations in intracellular ions (other than Ca 2+ ) or molecules may also explain spontaneous electrical activity. For example, increased [Ca 2+ ] i during an action potential might stimulate Na-Ca exchange and lead to a cyclic increase in [Na + ] i and thus an increase in the rate of Na + extrusion by the electrogenic Na-K pump.
what could activation of G-protein do (regard to spontaneous electrical activity)
may lead to formation IP3, thereby opening IP3R receptor channel and release Ca from SR. he rise in [Ca 2+ ] i would be self-reinforcing because CICR via RYRs ( Fig. 9-15 ) may propagate through the cell as a Ca 2+ wave.
what can inhibit RYR
high levels of Ca2+i SR Ca 2+ stores become depleted, or re-uptake of Ca 2+ into the SR occurs.
does reuptake of Ca2+ cost energy? in SR
yes
what is the junctional potential
the smooth muscle that regulates the iris of the eye, excitatory neurotransmitters such as norepinephrine and ACh cause a local depolarization
Action potentials usually do … in multiunit smooth muscle.
Action potentials usually do not occur in multiunit smooth muscle.
some unitary smooth muscle, including some vascular smooth muscle, also contracts as a result of …. changes.
ome unitary smooth muscle, including some vascular smooth muscle, also contracts as a result of graded V m changes.
what is the caveolae
rudimentary and shallow invaginations of the plasma membrane (smooth muscles version of T-tubules)
Smooth-muscle cells use three major pathways—not mutually exclusive—for producing the rise in [Ca 2+ ] i that triggers contraction
- Ca 2+ entry through L-type Cav channels in response to depolarization, (2) Ca 2+ release from the SR via RYR and IP 3 R Ca 2+ -release channels, and (3) Ca 2+ entry through voltage-independent/store-operated channels.
What activates the RYR3 subtype of ryanodine receptors and causing CICR
Ca 2+ entry through small clusters of the Cav1.2 variant of L-type channels,
Whereas the rise of [Ca 2+ ] i via CICR is a prominent aspect of cardiac muscle, the receptor-mediated… pathway is particularly significant for SR Ca 2+ release in smooth muscle.
Whereas the rise of [Ca 2+ ] i via CICR is a prominent aspect of cardiac muscle, the receptor-mediated IP 3 pathway is particularly significant for SR Ca 2+ release in smooth muscle.
is the relationship between plasma mebrane and SR as regular in smooth mucle as the triads and dyads?
no
what is the peripheral SR compartment
encircles the invaginating plasma membrane—forming a gap of only 15 nm—facilitating Ca 2+ diffusion and thus CICR.
what is the role of the central SR in smooth muscle
A larger network of central SR runs along the long axis of the cell, playing greater role in delivering Ca 2+ to intracellular myofilaments for contraction.
what is different from smooth and cardiac muscle in regard to rise in [Ca 2+ ] i
in smooth, the rise in [Ca 2+ ] i stimulates Ca 2+ -activated ion channels other than RYR (e.g., Ca 2+ -activated K + channels and Ca 2+ -activated Cl − channels) that participate in repolarization and regulation of contractile tone.
what cells lack Cav channel?
secretory epithelia, mast cells, and lymphocytes
What is Ca release activated Ca current (iCRAC)
depletion of Ca 2+ from ER storage compartments may trigger Ca 2+ influx through the plasma membrane, followed by the active uptake of this Ca 2+ into the ER to replenish the Ca 2+ store.
What is kind of channels is the Orai
store-operated calcium channel
what do store operated calcium entry (SOCE) rely on
is activated in response to depletion of the endoplasmic reticulum-Ca2 + store
what causes severe combined immunodeficiency syndrome
Missense mutations in the human ORAI1 gene eliminate the I CRAC
in what kind of cells is the Orai channel is under the control of the Ca 2+ -sensing STIM protein in ER membrane
non exitable
what supresses STIM
As ER [Ca 2+ ] rises, Ca 2+ again binds to the site on STIM
what happens When ER [Ca 2+ ] is depleted and Ca 2+ dissociates from a binding site on the N terminus of STIM?
causes STIM to aggregate in regions of the ER membrane that are closely associated with the plasma membrane. This STIM aggregation then triggers a direct interaction of the cytosolic C terminus of STIM with a coiled-coil domain on the cytosolic C terminus of Orai tetramers. The result is a clustering of Orai tetramers to form active Ca 2+ channels that mediate Ca 2+ influx across the plasma membrane and subsequent refilling of the ER stores.
SOCE is clearly involved in the Ca 2+ -dependent regulation of smooth-muscle contraction. Many types of smooth muscle express …. proteins.
SOCE is clearly involved in the Ca 2+ -dependent regulation of smooth-muscle contraction. Many types of smooth muscle express STIM and Orai proteins.
DO Ca 2+ release from the SR and the entry of Ca 2+ via SOCE need voltage?
NO
what is pharmacomechanical coupling?
Form of EC coupling in which intracellular release of Ca 2+ is initiated by chemical activators rather than membrane voltage changes. (SOCE)
what makes pharmacomechanical make possile?
a variety of drugs, excitatory neurotransmitters, and hormones can induce smooth-muscle contraction by these coupling mechanisms independently of action potential generation, as discussed in the previous section, and also independently of direct changes in [Ca 2+ ] i ,
What are dense bodies
specialized loacations in the smooth muscle cell where multiple actin filaments are joinded
why is smooth muscle not striated
because smooth-muscle actin and myosin are not as highly organized as in skeletal and cardiac muscle
what do cell bodies contain and are similar to?
α-actinin and are analogous to the filament-organizing Z lines of striated muscle.
what is different about thick ligaments in smooth m
Thick filaments are interspersed among the thin filaments in smooth muscle and are far less abundant than in skeletal or cardiac muscle.
What is calmodulin (CaM)
binding site for four Ca ions, closely related to troponin C of striated muscle
what does the Ca 2+ -CaM complex activate?
an enzyme known as myosin light chain kinase (MLCK)
what does myosin light chain kinase (MLCK) do?
phosphorylates the regulatory light chain that is associated with each neck of the dimeric myosin II heavy chain
what does Phosphorylation of the light chain cause?
a conformational change of the myosin head, which increases the angle between the head and neck domain of myosin and also increases its ATPase activity, allowing it to interact efficiently with actin and act as a molecular motor.
When can in smooth muscle contraction start? (after binding Ca)
contraction cannot begin until MLCK increases the ATPase activity of myosin, which is a relatively slow, time-dependent process.
what do caldesmon and Calponin do
inhibit the interaction between actin and myosin.
What does the Ca 2+ -CaM complex do to colponin
irst, Ca 2+ -CaM binds to calponin. Second, Ca 2+ -CaM activates CaMKII, which phosphorylates calponin. Both effects relieve calponin’s inhibition of myosin’s ATPase activity.
is the frequency of smooth muscle faster in smooth M?
no slower
Even though cross-bridge cycling occurs less frequently in smooth muscle, force generation may….
as great or greater, perhaps because the cross-bridges remain intact for a longer period with each cycle.
Why is myosin light chain phosphatase (MLCP) needed
Because Ca 2+ triggers smooth-muscle contraction by inducing phosphorylation of the myosin regulatory light chain rather than by simple binding to troponin C as in striated muscle, merely restoring [Ca 2+ ] i to its low resting value does not produce muscle relaxation.
what does myosin light chain phosphatase (MLCP) do.
dephosphorylate the myosin light chains, so the muscle can relax.
Ca 2+ -independent contractions may result either from….
n increase in the rate of MLC phosphorylation by MLCK or from a decrease in the rate of MLC dephosphorylation by MLCP.
What does prtein kinase C do?
decrease the activity of phosphatases
what are two examples of pharmacomechanical coupling (hint:MLCP and IP3)
Some excitatory stimuli are therefore capable of initiating smooth-muscle contraction by inducing IP 3 -mediated release of Ca 2+ from intracellular stores as well as by producing PKC-mediated decreases in MLCP activity.
ontractile force in smooth muscle largely depends on?
balance between the phosphorylation and dephosphorylation of MLCs.
Smooth-muscle cells can regulate [Ca 2+ ] i over a wider range than skeletal and cardiac muscle for several reasons. name them
smooth-muscle cells that do not generate action potentials—but rather exhibit graded V m responses to neurotransmitters or hormones—are able to fine-tune Ca 2+ influx via voltage-gated channels. Second, release of Ca 2+ from intracellular stores may be modulated via neurotransmitter-induced generation of intracellular second messengers such as IP 3 . This modulation allows finer control of Ca 2+ release
second level of control over contractile force occurs by regulation of the … sensitivity of proteins that regulate contraction.
second level of control over contractile force occurs by regulation of the Ca 2+ sensitivity of proteins that regulate contraction.
For example, inhibiting MLCP alters the balance between phosphorylation and dephosphorylation, in effect allowing a greater contraction at a lower [Ca 2+ ] i
Phosphorylation of MLCK by several protein kinases—including PKA, PKC, and CaMK—decreases the sensitivity of MLCK to activation by the Ca 2+ -CaM complex.
what is latch state
smooth muscle is able to maintain high force at a low rate of ATP hydrolysis. This low energy consumption/high-tension state is referred to as the latch state.
in the latch state is there higher or lower level of MLCK phosphorylation
lower
smooth muscle appears to be able to … cross-bridge cycling just before detachment, a feat that can be accomplished in skeletal muscle (see Fig. 9-7 ) only at low ATP levels (as in rigor mortis ).
mooth muscle appears to be able to slow down cross-bridge cycling just before detachment, a feat that can be accomplished in skeletal muscle (see Fig. 9-7 ) only at low ATP levels (as in rigor mortis ).
how is the capillary net work surrounding slow twitch fibers
dense, Slow-twitch fibers are thinner
are type 1 slow or fast twitch?
slow
why do Slow-twitch fibers appear red?
large amount of the oxygen-binding protein myoglobin
Type 1 fatigue color metabolism mitochondra glycogen
Type 1 fatigue resistent color red metabolism oxidative mitochondra high glycogen low
Type 2a fatigue color metabolism mitochondra glycogen
Type 2a fatigue resitent color red metabolism oxidative mitochondra highest glycogen abundant
Type 2/2x fatigue color metabolism mitochondra glycogen
Type 2/2x fatigue fatigable color white (low myoglobin) metabolism glycolytic mitochondra fewer glycogen high
is oxidative metabolsim effiecient and fast?
slow but efficient
why do type 2a have contain abundant glycogen and have a greater number of mitochondria than slow-twitch fibers do
These features ensure adequate ATP generation to compensate for the increased rate of ATP hydrolysis in fast-twitch fibers
does each muscle have one twitch type or more of muscle?
each whole muscle is composed of fibers of each twitch type, with one twitch type predominating.
what is the myometrium
smooth muscle of the uterus.
do phenotype of smooth muscle change
yes with shifting demands.
For example, systemic arterial smooth-muscle cells … when the oxygen concentration around them decreases, whereas pulmonary arterial smooth muscle … when local oxygen concentration decreases
For example, systemic arterial smooth-muscle cells relax when the oxygen concentration around them decreases, whereas pulmonary arterial smooth muscle contracts when local oxygen concentration decreases
what do cardiac muscle AP have?
plateau
how does the junctional potential spread
in a graded fasion
what muscles can contract without AP, with graded potenital
unitary , some vascualar muscle
