[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Physiology](https://durgical.com/en/physiology/) › [Nerve and muscle](https://durgical.com/en/physiology/#s-nerve_muscle) › Smooth muscle contraction

[Physiology](https://durgical.com/en/physiology/) · [Nerve and muscle](https://durgical.com/en/physiology/#s-nerve_muscle)

# Smooth muscle contraction

- Mechanism
- Exam priority: medium

Smooth muscle in vessels, airways and gut squeezes slowly and can hold tone for hours using very little energy.

Updated 2026-11-01

Also called: Calmodulin–MLCK pathway, Latch state

**See it in 3D:** [Trachea](https://durgical.com/en/anatomy/trachea/) · [Stomach](https://durgical.com/en/anatomy/stomach/) · [Urinary bladder](https://durgical.com/en/anatomy/urinary-bladder/)

## Key points

- Ca²⁺–calmodulin activates MLCK → phosphorylated myosin light chain → cross-bridge cycling. No troponin.
- Ca²⁺ sources: voltage-gated L-type channels, receptor-operated channels, and SR release through IP₃ receptors (Gq → PLC → IP₃).
- Relaxation: myosin phosphatase (activated by NO → cGMP); β2-receptor cAMP lowers Ca²⁺ and MLCK activity.
- Ca²⁺ sensitization: RhoA/Rho kinase inhibits myosin phosphatase, raising force without more Ca²⁺.
- Latch state: dephosphorylated myosin stays attached and cycles slowly, holding tone with very little ATP.

## What it is

Smooth muscle lines blood vessels, airways, the gut, bladder and uterus. Its contraction is switched on when Ca²⁺ binds calmodulin and activates myosin light-chain kinase (MLCK), which phosphorylates myosin. Myosin phosphatase reverses this, so tone reflects the balance between the two, set by nerves, hormones, stretch and local factors such as nitric oxide.

## How it works, step by step

- A stimulus (α1 or M3 receptor agonist, stretch, depolarization) raises cytosolic Ca²⁺.
- Gq-coupled receptors activate phospholipase C, producing IP₃ (SR Ca²⁺ release) and DAG.
- Depolarization opens L-type Ca²⁺ channels, adding extracellular Ca²⁺.
- Four Ca²⁺ ions bind calmodulin; the complex activates myosin light-chain kinase.
- MLCK phosphorylates the regulatory light chain, enabling myosin to cycle on actin anchored to dense bodies.
- Myosin phosphatase removes the phosphate; slowly detaching heads give the latch state and sustained tone.
- Ca²⁺ is removed by SERCA, plasma membrane Ca²⁺-ATPase and Na⁺/Ca²⁺ exchange, and the muscle relaxes.

## Regulation

- *+* **Norepinephrine on α1 receptors (Gq)**: IP₃ and Ca²⁺ rise: vasoconstriction
- *+* **Acetylcholine on M3 receptors (Gq)**: Bronchoconstriction, gut and bladder contraction
- *+* **Stretch (myogenic response)**: Arterioles constrict when pressure rises (autoregulation)
- *−* **β2 agonists (Gs → cAMP)**: Lower Ca²⁺ and MLCK activity: bronchodilation
- *−* **Nitric oxide (cGMP)**: Activates myosin phosphatase: vasodilation

## Clinical notes

- Asthma: airway smooth muscle is hyperresponsive; inhaled β2 agonists relax it via cAMP, and anticholinergics block M3-driven constriction.
- Arterial hypertension: increased vascular tone and remodeling raise peripheral resistance; Ca²⁺ channel blockers and α1 blockers lower tone.
- Nitrates and phosphodiesterase-5 inhibitors act through the NO–cGMP pathway; combining them can drop blood pressure dangerously.

## Memory aid

Calmodulin calls the kinase; the phosphatase pays the bill for relaxation.

## Test yourself

Think of the answer, then tap the question to see it.

## How does a β2 agonist relax bronchial smooth muscle at the molecular level?

β2 receptors activate Gs and adenylyl cyclase; cAMP activates PKA, which lowers cytosolic Ca²⁺ and phosphorylates MLCK so it is less active. Less myosin phosphorylation means relaxation.

## Why can smooth muscle hold tone for hours while using far less ATP than skeletal muscle?

In the latch state dephosphorylated cross-bridges remain attached and detach very slowly, so force is kept with little cycling and little ATP use.

## Why are nitrates and phosphodiesterase-5 inhibitors dangerous together?

Nitrates raise cGMP via NO and PDE-5 inhibitors stop cGMP breakdown. The combined vasodilation can cause severe hypotension.

## How can vascular tone rise without any increase in cytosolic Ca²⁺?

Through Ca²⁺ sensitization: RhoA/Rho kinase inhibits myosin phosphatase, so myosin stays phosphorylated at the same Ca²⁺ level.

[Add to my cards (4)](https://durgical.app/estudiar/?add=/en/physiology/smooth-muscle-contraction/)

## See it in 3D

The structures of Durgical's 3D anatomy where it happens.

- [Trachea](https://durgical.com/en/anatomy/trachea/)
- [Stomach](https://durgical.com/en/anatomy/stomach/)
- [Urinary bladder](https://durgical.com/en/anatomy/urinary-bladder/)

## Related topics

- [Skeletal, cardiac and smooth muscle compared](https://durgical.com/en/physiology/skeletal-cardiac-and-smooth-muscle-compared/)
- [Adrenergic and cholinergic receptors](https://durgical.com/en/physiology/adrenergic-and-cholinergic-receptors/)
- [Sliding filaments and the cross-bridge cycle](https://durgical.com/en/physiology/sliding-filaments-and-the-cross-bridge-cycle/)
- [Sympathetic and parasympathetic effects on each organ](https://durgical.com/en/physiology/sympathetic-and-parasympathetic-effects-on-each-organ/)

## Related conditions

- [Asthma](https://durgical.com/en/conditions/asthma/)
- [Arterial hypertension](https://durgical.com/en/conditions/arterial-hypertension/)

## In Biochemistry

- [IP₃, DAG and calcium pathway](https://durgical.com/en/biochemistry/topics/ip-dag-and-calcium-pathway/)
- [G protein-coupled receptors and cAMP](https://durgical.com/en/biochemistry/topics/g-protein-coupled-receptors-and-camp/)
- [Cyclic AMP (cAMP)](https://durgical.com/en/biochemistry/molecules/cyclic-amp/)

[← All of physiology](https://durgical.com/en/physiology/)

Educational physiology content; not a diagnostic or treatment guide and no substitute for a health professional's advice. Values are approximate references. No doses are given.

Sources: [10.8 Smooth Muscle](https://openstax.org/books/anatomy-and-physiology-2e/pages/10-8-smooth-muscle) (OpenStax (Rice University), 2022); [Asthma](https://www.ncbi.nlm.nih.gov/books/NBK430901/) (StatPearls (NCBI Bookshelf), 2024); Hall JE. Guyton and Hall Textbook of Medical Physiology, 13th ed. (ch. 8). Reference book used to check facts; its text and figures are not reproduced (Elsevier, 2016).

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Representative model, for educational purposes only.

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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/physiology/smooth-muscle-contraction/
