Smooth Muscle Physiology

Smooth Muscle: Structure & Types - Not So Simple!

• Structure:
  • Spindle-shaped (fusiform) cells, single central nucleus.
  • No striations: actin & myosin arranged obliquely.
  • Dense bodies (anchor actin) & intermediate filaments (desmin, vimentin).
  • Caveolae (rudimentary T-tubules); poorly developed Sarcoplasmic Reticulum (SR).
  • Lacks troponin; uses calmodulin for $Ca^{2+}$ binding.
• Types:
  • Unitary (Visceral/Single-unit):
    • Cells coupled by gap junctions (syncytium).
    • Spontaneous pacemaker activity; stretch-sensitive.
    • Location: Gastrointestinal Tract (GIT), uterus, bladder, small vessels.
  • Multi-unit:
    • Each cell individually innervated; no/few gap junctions.
    • Fine, graded contractions; no spontaneous activity.
    • Location: Iris, ciliary muscle, piloerectors, large airways/arteries.

⭐ Smooth muscle contraction is regulated by calcium binding to calmodulin, not troponin.

Smooth Muscle Contraction: Mechanism - The Calcium Dance

• Initiation: ↑ cytosolic $Ca^{2+}$.
  • Sources: ECF (L-type $Ca^{2+}$ channels, ligand-gated channels) & SR (IP3-receptors).
• $Ca^{2+}$ Binding: $Ca^{2+}$ binds Calmodulin (CaM). (No troponin complex).
• MLCK Activation: $Ca^{2+}$-CaM complex activates Myosin Light Chain Kinase (MLCK).
  • 📌 CaMels Make Lovely Contractions (Calmodulin, MLCK, Myosin Light Chain).
• Myosin Phosphorylation: MLCK phosphorylates myosin light chains (MLC).
  • This enables myosin heads to bind actin & ↑ ATPase activity.
• Cross-bridge Cycling: Actin-myosin interaction → contraction. Slow, sustained, energy-efficient.
• Relaxation: ↓ cytosolic $Ca^{2+}$ (pumps); Myosin Light Chain Phosphatase (MLCP) dephosphorylates MLC.

⭐ Key feature: Latch-bridge mechanism. Myosin dephosphorylation by MLCP while attached to actin allows sustained contraction with low ATP use.

Smooth Muscle Regulation: Control - Who's the Boss?

• Neural Control (ANS):
  • Sympathetic (e.g., Norepinephrine via adrenergic receptors) & Parasympathetic (e.g., Acetylcholine via muscarinic receptors).
  • Neurotransmitters released from varicosities into diffuse junctions.
  • Response can be excitatory or inhibitory, receptor-dependent.
• Hormonal Control:
  • Circulating hormones: Angiotensin II, Vasopressin, Oxytocin, Epinephrine, Histamine.
  • Bind to specific membrane receptors (often G-protein coupled).
• Local Factors (Paracrine & Myogenic):
  • Paracrine signals: Nitric Oxide (NO), prostaglandins, histamine, endothelin.
  • Local chemical changes: ↓$O_2$, ↑$CO_2$, ↓pH, ↑K+.
  • Stretch-induced contraction (myogenic response).
  • Pharmacomechanical coupling: Contraction/relaxation without significant membrane potential change.

⭐ Many smooth muscles exhibit spontaneous electrical activity (slow waves, pacemaker potentials) leading to myogenic tone, an intrinsic control mechanism.

Smooth Muscle Electrophysiology: Potentials - Electrical Vibes

• Resting Membrane Potential (RMP): Unstable, typically -50 to -60 mV.
  • Influenced by Na⁺/K⁺ pump & ion channel activity.
• Action Potentials (APs):
  • Spike potentials: Rapid depolarization/repolarization (unitary smooth muscle).
  • APs with plateaus: Prolonged contraction (e.g., ureter, uterus); due to sustained Ca²⁺ influx.
  • Slow waves (pacemaker waves): Rhythmic, spontaneous depolarizations; can trigger APs if threshold is met.
• Ionic Basis:
  • Depolarization: Mainly Ca²⁺ influx (L-type Ca²⁺ channels), less Na⁺.
  • Repolarization: K⁺ efflux.

⭐ Interstitial Cells of Cajal (ICC) are the pacemakers generating slow waves in GI smooth muscle, not the smooth muscle cells themselves.

High‑Yield Points - ⚡ Biggest Takeaways

• Unitary smooth muscle: gap junctions for syncytial action; Multiunit: fine, independent control.
• Calmodulin is the key Ca²⁺-binding protein (troponin absent), initiating contraction.
• Contraction requires Myosin Light Chain Kinase (MLCK) activation by Ca²⁺-calmodulin, leading to myosin phosphorylation.
• The latch-bridge mechanism enables sustained tonic contraction with low ATP consumption.
• Characterized by slow, prolonged contractions, the stress-relaxation response, and significant plasticity.
• Regulated by ANS, hormones, and local chemical signals.