FORM AND FUNCTION (Smooth Muscle 2)

Question 1

At rest:

Answer 1

-myosin is in cocked position with ADP+P
-myosin light chains (MLC)

Question 2

Myosin light chains (MLC):

Answer 2

-crossbridge cycle initiation depends on MLC phosphorylation
-MLCK catalyzes its phosphorylation
-myosin phosphatase catalyzes its dephosphorylations

Question 3

Myosin phosphatase

Answer 3

-catalyzes dephosphorylation of MLC
>ending the cycle
-always active ‘ON’

Question 4

MLCK:

Answer 4

-phosphorylates MLC
>starts the crossbridge cycle
-regulated by Ca2+ levels

Question 5

Ca2+ levels and MLCK:

Answer 5

-high: active
-low: inactive (myosin phosphatase removes the P)

Question 6

Sustained muscle contraction mechanism:

Answer 6

-dephosphorylation of MLC during the crossbridge cycle slows down the cycle, causing a ‘latch state’
>tension remains while the crossbridge is attached (similar to rigor mortis)
*one cycle uses one ATP

Question 7

Rigor mortis:

Answer 7

-when you run out of ATP

Question 8

‘latch bridge’:

Answer 8

-due to low Ca2+
-when the myosin head is attached but the MLC is not phosphorylated
-sustains force with less ATP consumption

Question 9

More crossbridge that are ‘latch bridge’:

Answer 9

-rise in contraction in the sustained state

Question 10

Phasic contraction:

Answer 10

-stimulation: Ca2+ increase and then back to base level
-Ca2+ followed by cross-bridge phosphorylation and then force
*all increase and go back to base line

Question 11

Tonic contraction:

Answer 11

-stimulation
-increase Ca2+, decreases slightly and then ‘plateaus’
-increase in cross-bridge phosphorylation and then ‘plateaus
-low rate of Ca2+-dependent phosphorylation of MLC is still essential for contraction

Question 12

Summary of molecular mechanisms of smooth muscle contraction:

Answer 12

1. Smooth muscle contractions are mainly ‘thick filament-regulated’
2. Latch bridge hypothesis
3. Smooth muscles can produce greater force than skeletal muscle due to prolonged attachment of cross-bridges

Question 13

Thick filament-regulated:

Answer 13

-MLC phosphorylation is required for myosin-actin interaction
>dependent on the activities of MLCK and myosin phosphatase (MP)
-MLCK activity is regulated by calcium
-MP is always ON

Question 14

Latch bridge hypothesis:

Answer 14

-latch forms when MLC is dephosphorylated by MP while attached to the myosin head, contributing to sustained force during tonic contraction
>uses less energy than skeletal muscle to generate the same force

Question 15

Length-tension relationship: smooth muscle

Answer 15

-can shift the length-tension curve depending on the resting length
-if stretched=the length-tension curve will shift to LONGER lengths over the course of minutes to hours
*due to increased number of contractile unit in series

Question 16

Force and velocity relationship

Answer 16

-same inverse relationship between force and shortening velocity but Vmax in smooth muscle is much SLOWER
-can be regulated by nerve stimulus and hormones
-intracellular calcium concentration impacts MLC phosphorylation

Question 17

Higher percentage of phosphorylation:

Answer 17

-increases smooth muscle contractility
>similar effect to increase inotrophy in cardiac muscle

Question 18

Smooth muscle metabolic demands:

Answer 18

-least out of the three muscle types
>latch bridge
>also slower

Question 19

NT and receptors: smooth muscle

Answer 19

-muscarinic cholinergic receptor (M)
-E/NE receptors (alpha-adrenergic and beta-adrenergic)

Question 20

Varicosities:

Answer 20

-axon-like swellings on autonomic nerve fibers
-release their NT into a wide synaptic cleft (a diffuse junction)

Question 21

Modulation of smooth muscle activity by:

Answer 21

-NT
-hormones
-local factors

Question 22

NT, hormones and local factors:

Answer 22

-activates contraction by increasing cellular Ca2+
-multiunit: no electrical coupling and neural regulation is important
-single unit: electrical activity is propagated throughout the tissue
*most smooth muscle is probably between the spectrum of multi and single unit

Question 23

Smooth muscle adaptation:

Answer 23

-hyperplasia
-hypertrophy

Question 24

Hyperplasia: smooth muscle

Answer 24

-retain the capacity to divide
-prominent during development and growth phases

Question 25

Hypertrophy: myometrium

Answer 25

-uterine smooth muscle
-enlarges as birth approaches
-hypertrophy and large number of gap junctions form just before birth

Question 26

Hypertrophy: compensatory response

Answer 26

-compensatory response to increased mechanical work
-polyploid cells (DNA replication without cell division) produce more contractile proteins, enhancing muscle function
Ex. arterial smooth muscle cells in hypertensive patients