Lecture 7: Smooth Muscles

Question 1

What are the differences between smooth and skeletal muscle contraction?

Answer 1

• Actin and myosin filaments are longer in smooth muscle
• smooth muscle myosin thick filaments have no bare zone- can slide along actin for long distance
• smooth muscle myosin has slower rate of crossbridge cycling (–> slower contraction phase)

Question 2

What are the 2 different types of smooth muscle fibre types?

Answer 2

They are separated by the degree of gap junction coupling and pattern of innervation (nerve supply) slide 19

1. Single unit
   - gap junction coupling (syncytium)
   - innervated by relatively few neurons, signal spreads
   - located in urogenital and gastrointestinal tracts
   - typically, phasic contractions
   - contracts as a single unit
2. Multi unit
   - no gal junction coupling
   - richly supplied with neurons
   - located in respiratory airways, blood vessels and iris of eye
   - typically, tonic contractions

Question 3

What is the different electrical and contractile activity of single and multi-unit smooth muscle?

Answer 3

RMP of smooth muscle cells is unstable (unlike skeletal muscle)
Single unit:
-RMP shows oscillations called slow waves
-spontaneous, large regular fluctuations in RMP
-propagated by gap junctions due to:
a) phasic activity of Na+/K+ pump
b) variations in membrane Na+ and K+ permeability
-phasic contraction: fast maintained for short periods of time

Multi unit

• RMP unstable but reasonably steady
• Tonic contractions (slower, maintained for longer)

Question 4

We’re is smooth muscle found?

Answer 4

Usually found in the walls of hollow tubes
Ie blood vessels, airways, gut, reproductive tract
Contraction changes organ shape and squeezes contents along

Question 5

Now is smooth muscle different from cardiac and skeletal?

Answer 5

Slower, can be sustained for longer, requires less energy (per unit force)

Question 6

Describe the structure of smooth muscle cells

Answer 6

Small spindle-shaped cells

• single central nucleus
• bundles of actin and myosin filaments extend diagonally
• cells become globular during contraction
• no distinct striations like skeletal
• no T-tubules

Question 7

What are the structural features if smooth muscle cells
Gap junctions
Dense bodies
Attachment plaques
Intermediate filaments

Answer 7

Gap junctions:
-allows passage of chemicals and electrical signals
Dense bodies
-proteins attachments between thin filaments and intracellular connective tissue (like z lines)
Attachment plaques:
-proteinaceous regions of cell membrane
-thin filaments extend into plaques
-form mechanical junctions
-allow transmission of force between cells
-also called adherens junctions, membrane dense area
Intermediate filaments:
-non-contractile filaments that resist tension
-attach to dense bodies/ attachment plaques

Question 8

What are the mechanisms of smooth muscle contraction and relaxation. Ie the major steps

Answer 8

Excitation:
-triggering of muscle Ca2+ elevation
Note: trigger is Ca2+ elevation, not AP firing. AP firing is not always required for smooth muscle contraction (unlike skeletal muscle)
Excitation-contraction coupling:
-triggering of contraction by muscle Ca2+ elevation
Contraction (crossbridge cycle)
-movement and/or force generation by muscle fibres
Relaxation:
-termination of movement and/or force generation by muscle fibres

Question 9

Describe in details the sequence of events for 
a) excitation of smooth muscle.
B) excitation-contraction coupling 
C) contraction (cross bridge cycle) 
D) relaxation

Answer 9

A) Trigger for contraction Ca2+ elevation, most often involving Ca2+ entry from extracellular space
-via ligand, voltage or mechanically gated channels
-initiated by many different signals
1- spontaneous activity of pacemaker smooth muscle cells
2- stretch of smooth muscle
3- neurally released transmitters
4- circulating hormones or locally generated paracrines chemicals
Note: decreased Ca2+ entry inhibits smooth muscle contraction (compare skeletal muscle)

B)
1- Ca2+ enters cell through gated-ion channels
2-Ca2+ entry triggers Ca2+ release from sarcoplasmic retic
3- Ca2+ binds to calmodulin (CaM)
4- Ca2+ CaM activates MLCK
5- MLCK phosphorylates myosin light chains –> increased myosin ATPase activity
6- Activated Myosin starts crossbridge cycling
Note: in smooth muscle, contraction is regulated by myosin, not actin as in skeletal muscle (Ca2+ targets thick not thin filaments)
New players in excitation-contraction coupling
Calmodulin (CAM)- cytoplasmic Ca2+ binding protein
Myosin light chain kinase
-cytoplasmic enzyme that acts on myosin light chains, it adds phosphate from ATP and turns on myosin ATPase activity
C) contraction/ crossbridge cycle
-smooth muscle specialised for slower sustained contractions
-slowest contraction/relaxation times of all muscle types
-smooth muscle able to sustain contractions for extended periods without fatiguing.
D) relaxation
-Ca2+ pumped out of cell or into SR, decreasing cytoplasmic Ca2+
-Ca2+ unbinds from calmodulin (CaM), inactivating MLCK
-myosin phosphatase removes phosphate from myosin, decreasing myosin ATPase activity
-reduced myosin ATPase activity –> less crossbridge cycling