Smooth Muscle Contraction and Relaxation

Overview

• Smooth muscle contraction and relaxation processes are distinct from those in skeletal muscle.
• No neuromuscular junction in smooth muscle; contraction can be triggered by neurons, hormones, or stretch.
• Focus on calcium's role in initiating contraction and relaxation.

Contraction Initiation

Stimulus and Calcium Channels

• Stimulus: Triggered by various mechanisms (e.g., chemical, mechanical), leading to calcium channel activation.
• Calcium Channels: Could be chemically or mechanically gated, leading to influx of extracellular calcium.

Molecular Process

• Phospholipase C (PLC): Activated by calcium, breaking phospholipids into Inositol Triphosphate (IP3) and Diacylglyceride (DAG).
  • IP3: Acts as a secondary messenger, significant for this process.

Calcium Release

• Sarcoplasmic Reticulum (SR): Less branched than in skeletal muscle, stores calcium.
• IP3 Mediated Calcium Channel: IP3 binds, opening the channel and releasing calcium from SR into cytosol.

Calcium Binding and Enzyme Activation

• Calmodulin (CaM): Calcium binds to CaM, forming a CaM-Ca2+ complex.
• Myosin Light Chain Kinase (MLCK): Activated by CaM-Ca2+ complex.

Myosin Activation

• Myosin Structure: Actin binding site, ATPase domain, and activation site.
• Phosphorylation: MLCK adds phosphate to activation site, initiating the power stroke.
• Calcium-Induced Calcium Release (CICR): Extracellular calcium influx triggers intracellular calcium release.

Contraction Sequence

1. Stimulus triggers extracellular calcium influx.
2. Triggers intracellular calcium release from SR.
3. Calcium binds to calmodulin.
4. Activates MLCK, which phosphorylates myosin.
5. Initiation of power stroke.

Relaxation Process

Calcium Removal

• Calcium ATPase: Present in SR and plasma membrane, moves calcium from cytosol to SR or interstitial fluid.
• Sodium-Calcium Antiporter: Uses sodium gradient to expel calcium from cytosol to interstitial fluid.

Reduction in Calcium-Calmodulin Complex

• As cytosolic calcium decreases, the calcium-calmodulin complex reduces.
• Without this complex, MLCK is inactivated.

Dephosphorylation

• Myosin Light Chain Phosphatase (MLCP): Removes phosphate from myosin.
  • Active at low levels at rest.
  • MLCK rephosphorylates myosin rapidly during contraction.

Relaxation Sequence

1. Removal of calcium from the cytosol stops activation of MLCK.
2. MLCP removes phosphate from myosin.
3. End of power stroke.

Summary of Smooth Muscle Contraction and Relaxation

• Smooth muscle contraction involves the sustained presence of phosphate on myosin due to the balance of kinase and phosphatase activity.
• Relaxation involves a protracted removal of calcium and phosphate, leading to a more sustained contraction and relaxation cycle compared to skeletal muscle.