Pharmacology - Smooth Muscle

Question 1

Role of smooth muscle

Answer 1

contraction and relaxation of hollow organs and regulation of flow by:

• varying tube diameter (blood vessels during exercise)
• occluding tube (sphincters)
• walls of storage organ (bladder)
• movement of laarge bulk (oesophagues)
• vascular system –> hypertension
• airways –> asthma
• GIT –> gastric spasticity, IBS
• Urinogenital tract –> infetility
• Eye

Question 2

Smooth muscle structure

Answer 2

• not attached to structure and no tendons
• small cells (do not extend full length of muscle)
• single sheet: circularly oriented (arterioles) –> control blood flow
• multiple sheets perpendicular to each others, longitudinal and circular (ileum) –> vary diameter & length (peristalsis)

Question 3

Smooth muscle cell structure

Answer 3

• small, spindle-shaped
• uni-nucleaate
• not banded, no striations
• no z-bands of cyto-skeletal proteins, but dense bodies
• actin filaments anchored to ‘dense bodies’
• myosin filaments presents

Question 4

Smooth muscle contraction

Answer 4

latch phenomenon –> actin and myosin remain contracted without fatigue

Question 5

Sliding filament theory

Answer 5

1) myosin head domain bound to ATP, no interaction
2) ATP –> ADP & phospahte, myosin head interact with actin
3) Lose ADP & phospahte, myosin moves along actin
4) ATP comes in, repeat process

Question 6

Innervation of smooth muscle

Answer 6

• neurotransmitter receptors over the muscle surface

- variscosities

Question 7

Cell-cell communication

Answer 7

gap junctions:

• couple smooth muscle cells to one another
• propagate signals between cells
• synchronised contraction and relaxation

Question 8

Calcium in smooth muscle contraction

Answer 8

Calcium sources:

• Ca2+ influx across plasma membrane from outside cell, regulated by voltage gated Ca2+ channels
• Ca2+ mobilisation from intracellular stores, through activation of 2nd messenger (ex: ACh acting on M3 receptors –> IP3 release –> Ca2+ release)

Varying intracellular Ca2+ enable smooth muscle to vary level of contraction

Increasing Ca2+ increases level of tone by increasing contraction of smooth muscle cells

Question 9

Contraction mechanism of smooth muscle

Answer 9

1) Ca2+ + Calmodulin –> Calcium calmodulin complex –> activates myosin light chain kinase (MLCK)
2) MLCK: MLC –> MLC-Phos
3) + actin –> contraction

Rho kinase –> inhibit MLCP

Question 10

Relaxation mechanism of smooth muscle

Answer 10

myosin light chain phosphotase (MLCP): MLC-Phos –> MLC

cAMP –> protein kinase A (PKA) –> inhibit MLCK

cAMP –> activate MLCP

cGMP –> activate MLCP

examples:
β-adrenoceptors –> increase cAMP in smooth muscle –> relaxation of airways

Nitric oxide –> cAMP –> relaxation of vascular smooth muscle

Question 11

smooth muscle tone

Answer 11

balance regulated by contractile and relaxatory agents released from different areas