Smooth muscles

[Ref: WG21:Chp3,p583]

Types

• Visceral type
  * syncytial
  * e.g. walls of hollow viscera, arteriole
• Multi-unit type
  * nonsyncytial
  * contraction more fine and localised
  * e.g. iris

 

Differences (visceral vs skeletal)

Structural

• Not arranged in regular arrays
  --> striation absent
• Contains tropomyosin, but no troponin
• No fast Na+ channels
• Sarcoplasmic reticulum poorly developed (but still plays a role in contraction/relaxation)
• Lacks transverse tubules
• Smaller number of myosin
• Few mitochondria
• Mainly glycolysis

Ionic

• Membrane potential unstable
• No true resting value of Vm
  * i.e. No true RMP

Functional

• Syncytial
  * like cardiac muscles
  * via gap junctions
• No voluntary control
• More sensitive to circulating chemical mediators
• Spontanenous electrical activity
• Contracts spontaneously when stretched
• Continuous, irregular contraction independent of nerve supply

Contraction

• Lag between stimulation and contraction
  * No close excitation-contraction coupling
• Myosin must be phosphorylated for activation of the myosin ATPase
• Plasticity
  * Variability of tension at any given length
  * No strict correlation between tension and length

Excitation-contraction coupling (???? Visceral only)

[WG21:Chp3 - visceral smooth muscles]

Contraction

Binding of acetylcholine to muscarinic receptors

--> Increased Ca2+ influx
* Primarily from ECF via voltage-gated and ligand-gated Ca2+ channels
* Predominantly ligand-gated Ca2+ channels in the sarcolemma

--> Ca2+ binds to calmodulin

--> Ca2-calmodulin complex activates calmodulin-dependent myosin light chain kinase (MLCK)

--> MLCK catalyze phosphorylation of myosin light chain

--> Myosin light chain activated

--> Actin slides on myosin

--> Contraction

 

NB:

• In skeletal muscles and cardiac muscles, contraction is triggered by binding of Ca2+ to troponin C
• cAMP causes relaxation of smooth muscles (due to inhibition of MLCK)
• In contrast, cAMP increases contractility of cardiac muscles

 

Relaxation

Myosin is dephosphorylated by myosin light chain phosphatase

--> Relaxation does not necessarily occur

Other mechanisms are involved in relaxation

NB:
Myosin light chain phosphatase is inhibited when phosphorylated, and activated when dephosphorylated

Latch bridge mechanism

Myosin cross-bridge remain attached to actin after cytoplasmic [Ca2+] falls

--> Contraction is often tonic

 

Vascular smooth muscles

Ganong [WG21:p582]

In Ganong, it seems to be suggesting vascular smooth muscles and visceral smooth muscles are slightly different.

Also that SR plays an important role in relaxation.

Thus,

Ca2+ influx from ECF via voltage-gated Ca2+ channels

--> Diffuse increase in intracellular [Ca2+]

--> Contraction initiated

However,

Ca2+ influx also triggers Ca2+ release from SR via ryanodine receptors

--> High local [Ca2+]

--> Activates Ca2+-activated K+ channels (Big K or BK)

--> Increase K+ efflux via BK channels

--> Increase Vm

--> Voltage-gated Ca2+ channel closed

--> Relaxation

Berne and Levy [BL8:p178-179]

In Berne and Levy, it seems to be suggesting that:

• SR is also important
• Ca2+ released by SR causes contraction
  * i.e. Not relaxation via BK channels
• Release of Ca2+ from SR is via IP3
  * Not via ryanodine receptors

Thus, the sequence of events is:

Agonist activates a receptor in the vascular smooth muscle membrane

--> Activation of phospholipase C via Gq-protein

--> PIP2 --> DAG + IP3

--> IP3 causes release of Ca2+ from SR

--> Contraction via Calmodulin, MLCK, etc

Relaxation is by reduction of [Ca2+]

 

Effect of ANS

[WG21: p84-85]

Epinephrine and norepinephrine

Vm more negative

--> Decrease spike frequency

--> Relaxation

 

Stimulation of beta-adrenergic

--> Increased cAMP (probably due to increased intracellular [Ca2+] binding)

--> Inhibition of MLCK

--> Relaxation

 

Stimulation of alpha-adrenergic

--> Increased Ca2+ efflux (how????)

--> Contraction inhibited

Acetylcholine on visceral smooth muscles

Vm less negative

--> Increase phospholipase C and IP3

--> Increased intracellular [Ca2+]

--> Spikes more frequent

--> Increased tonic tension and rhythmic contraction

NB:

• Parasympathetic stimulation tends to decrease vascular resistance, but they innervate only small fraction of the blood vessels