Week 6 - Smooth muscle regulation

2 forms of smooth muscle regulation

• Electric (electromechanical) regulation → membrane potential changes, contraction only

• Pharmacomechanical regulation → membrane potential does NOT change, contraction AND relaxation

Smooth muscle: Electric (electromechanical) regulation

• 3 methods of Ca2+ entry into smooth muscles

1. Voltage-gated Ca2+ channels - Triggered by membrane potential changes

2. Ligand-gated Ca2+ channels - Triggered by chemical signals

3. Stretch-activated channels - Triggered by stretch of membrane, Ca2+ enters

• Example:

  • Blood vessels are surrounded by smooth muscle cells

  • Stretch-activated channels

    • Increase in blood volume → increases blood pressure → smooth muscle cell membranes stretched → Stretch-activated channels open

    • Smooth muscle contraction results

Smooth muscle: Electric (electromechanical) regulation

• Slow wave potential

Membrane potential is COMPLEX in smooth muscle.

Smooth muscle membrane potentials can:

• Hyperpolarise

• Depolarise

Both without reaching threshold potential (consult diagram).

A cell has slow wave potentials when they have cyclic depolarization and repolarization of their membrane potential.

• allows a smooth muscle to “ride a wave” of potential

• If a stimulus is added, that pushes the wave to threshold potential, causing muscle contraction

E.g Intestines when empty, when food enters, stimulus pushes wave to threshold and contraction, pushing food through.

Smooth muscle: Electric (electromechanical) regulation

• Pacemaker potential

These are also found in cardiac muscle cells.

Establishes a regular rhythm.

Action potentials and contractions occur at a regular rhythm.

• Used in phasic contractions (e.g GI tract)

Smooth muscle: Pharmacomechanical regulation

3 forms of communication:

• Neurotransmitters → nervous system

• Hormones → endocrine system

• Paracrine signalling → neighbouring cells

Smooth muscle contraction occurs WITHOUT membrane potential changes.

• Pharmacomechanical regulation allows contraction AND relaxation

Smooth muscle: Pharmacomechanical regulation

Example:

• IP3 pathway - Causes contraction

Regulates intracellular release of Ca2+ from sarcoplasmic reticulum.

1. Neurotransmitters, hormones or paracrine signals interact with membrane receptors on smooth muscle cells

2. Increases intracellular IP3

3. IP3 opens IP3 channels on sarcoplasmic reticulum

4. Ca2+ released into smooth muscle cell cytosol

5. Causes muscle contraction

Smooth muscle: Pharmacomechanical regulation

Example:

• MCLP & Ca2+sensitivity - Causes contraction OR relaxation

MLCP controls Ca2+ sensitivity:

• Increase in MCLP (phosphatase) activity → Decreases myosin-ATPase activity → Decreases muscle force → muscle relaxation

• Decrease in MCLP (phosphatase) activity → Increases myosin-ATPase activity → Increases muscle force → muscle contraction

MCLP activity can be influenced by Pharmacomechanical regulation (Neurotransmitters, hormones or paracrine signals)

Smooth muscle: Pharmacomechanical regulation

• Neurotransmitters - Causes contraction OR relaxation

Neurotransmitters from the autonomic nervous system (parasympathetic & sympathetic)

• Acetylcholine (Ach)

• Adrenaline

  • 2 receptors: ⍺ or β receptors

    • ⍺-receptors - Causes contraction - sympathetic nervous system

      • muscles of Blood vessels; radial dilator muscle of the eye; GI tract and bladder sphincters; pregnant uterus

    • β-receptors - Causes relaxation - parasympathetic nervous system

      • muscles of Airways; walls of stomach, small intestine, and bladder; some blood vessels

Smooth muscle: Pharmacomechanical regulation

• Neurotransmitters

Hormones from the endocrine system (long-term signalling)

• Angiostenin 2

Smooth muscle: Pharmacomechanical regulation

• Paracrine signals

Paracrine signals from the neighbouring cells

• Histamine

  • Activates IP3 pathway - Causes contraction

    • Contraction of airways, think allergies, anaphylaxis

• Nitric oxide

  • Manages vasoconstriction & vasodilation

  • Increasing nitric oxide → Causes relaxation

• K+ ions

  • Put into bloodstream during exercise (by-product of skeletal muscle use)

  • Muscles require more oxygenated blood

  • K+ causes vasodilation → Causes relaxation

K+ ions and nitric oxide work in tandem.