M04.05.009 Smooth muscle: Actin-Myosin Interaction

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Learning Objective

Describe how smooth muscle contraction is regulated by calcium–calmodulin–mediated phosphorylation of myosin light chains and compare this mechanism to contraction in striated muscle.

Overview Of Smooth Muscle Contraction

Smooth muscle generates tension through actin–myosin interaction, similar to skeletal and cardiac muscle.

However, unlike striated muscle, smooth muscle:

❌ Does not contain troponin
❌ Does not use tropomyosin to regulate contraction
✔️ Regulates contraction through myosin phosphorylation

Contraction in smooth muscle depends on the phosphorylation state of myosin light chains (MLC).

Resting State Of Smooth Muscle

In resting smooth muscle:

Myosin light chains (MLC) are not phosphorylated
Myosin has low affinity for actin
Cross-bridge formation does not occur
Muscle remains relaxed

Activity

Initiation Of Contraction

Smooth muscle contraction begins when cytosolic Ca²⁺ increases.

Sources Of Ca²⁺ Increase:

Extracellular Calcium Entry
1. Depolarization opens L-type voltage-gated Ca²⁺ channels
2. Ca²⁺ enters the cytosol
Calcium Release From SR
1. Calcium-induced calcium release
IP₃-Mediated Release
1. An agonist binds a Gq-coupled receptor (e.g., α₁ receptor)
2. IP₃ increases
3. Ca²⁺ released from sarcoplasmic reticulum

Activity

Calcium–Calmodulin Pathway

Once intracellular Ca²⁺ rises:

Step	Process
1	Ca²⁺ binds to calmodulin (CAM)
2	Ca²⁺–CAM complex activates MLCK
3	MLCK phosphorylates the myosin light chain
4	Phosphorylated myosin binds actin
5	Cross-bridge cycling begins
6	Smooth muscle contraction occurs

Maintenance Of Contraction

ATP is required to detach actin from myosin
If MLC remains phosphorylated:
- Cross-bridge cycling continues
- Tension is maintained

High cytosolic Ca²⁺ → MLCK activity predominates → Contraction

Relaxation Of Smooth Muscle

Relaxation occurs when cytosolic Ca²⁺ decreases.

Mechanism

Activation of myosin light-chain phosphatase (MLCP)
MLCP dephosphorylates myosin
Myosin loses affinity for actin
Cross-bridges detach
Muscle relaxes

Low cytosolic Ca²⁺ → MLCP activity predominates → Relaxation

Comparison With Striated Muscle

Feature	Smooth Muscle	Striated Muscle
Troponin	Absent	Present
Regulation	Myosin phosphorylation	Actin binding site exposure
Calcium Binds To	Calmodulin	Troponin-C
Key Enzyme	MLCK	Myosin ATPase
Trigger For Contraction	MLC phosphorylation	Troponin activation
Relaxation Mechanism	MLCP activation	Ca²⁺ reuptake into SR