Part 4 · Chapter 4.3

Smooth Muscle

Smooth muscle is non-striated, involuntarily controlled, and operates under fundamentally different regulation from striated muscle: contraction is activated via myosin-light-chain kinase (MLCK) phosphorylation rather than troponin-C Ca²⁺ binding. This chapter covers MLCK/MLCP dynamics, Ca²⁺sensitisation via Rho kinase, and visceral smooth-muscle function.

1. MLCK Pathway

Cytosolic Ca²⁺ binds calmodulin (CaM); Ca²⁺₄-CaM activates myosin-light-chain kinase (MLCK); MLCK phosphorylates Ser19 of the regulatory myosin light chain (MLC); phosphorylated myosin cycles cross-bridges on actin:

\[ \text{Ca}^{2+} \to \text{CaM} \to \text{MLCK} \to \text{pMLC}_{\text{Ser19}} \to \text{contraction} \]

Myosin-light-chain phosphatase (MLCP) dephosphorylates pMLC and relaxes the muscle. The force is set by the MLCK/MLCP ratio, not by Ca²⁺ alone.

2. Ca²⁺ Sensitisation

Rho kinase (ROCK) phosphorylates MYPT1 (MLCP regulatory subunit), inhibiting MLCP. This shifts the MLCK/MLCP balance toward phosphorylation, producing force at lower Ca²⁺ — so-called Ca²⁺ sensitisation. G_q (via RhoGEF) and G_12/13 activate Rho. Fasudil and Y-27632 are Rho-kinase inhibitors; sildenafil indirectly opposes this via cGMP.

Simulation: Ca-MLCK-Force Coupling

Python

script.py33 lines

import numpy as np, matplotlib
matplotlib.use('Agg')
import matplotlib.pyplot as plt

# MLCK pathway: Ca/CaM -> MLCK -> phosphorylated MLC -> cross-bridge cycling
Ca = np.logspace(-8, -5, 200)
CaM = 1e-5
Kd_Ca_CaM = 1e-6
CaCaM = Ca*CaM / (Kd_Ca_CaM + Ca)
# Activated MLCK = fraction Ca4CaM bound to MLCK
MLCK_active = CaCaM / (CaCaM + 1e-7)
# Phosphorylated MLC depends on balance with MLCP
MLCP = 0.3   # constant, baseline
pMLC = MLCK_active / (MLCK_active + MLCP)
# Force ~ pMLC
Force = pMLC**2 / (pMLC**2 + 0.25)

fig, ax = plt.subplots(figsize=(11, 6), facecolor='#0a0f1e')
ax.set_facecolor('#111e2f'); ax.tick_params(colors='#bae6fd')
for s in ax.spines.values(): s.set_color('#334155')
ax.semilogx(Ca*1e6, MLCK_active, color='#60a5fa', lw=2.4, label='Active MLCK')
ax.semilogx(Ca*1e6, pMLC, color='#fbbf24', lw=2.4, label='Phosphorylated MLC')
ax.semilogx(Ca*1e6, Force, color='#f87171', lw=2.6, label='Force')
ax.set_xlabel('[Ca2+] (uM)', color='#bae6fd')
ax.set_ylabel('Fractional activation', color='#bae6fd')
ax.set_title('MLCK pathway Ca-force coupling',
             color='#67e8f9', fontweight='bold')
ax.legend(facecolor='#1e293b', edgecolor='#334155', labelcolor='#cbd5e1')
ax.grid(True, color='#334155', alpha=0.3, which='both')
plt.tight_layout()
plt.savefig('output.png', dpi=120, bbox_inches='tight', facecolor='#0a0f1e')
print('Smooth muscle force depends on pMLC, governed by MLCK/MLCP balance')
print('Ca sensitisation: Rho kinase inhibits MLCP -> force at fixed Ca rises')

Click Run to execute the Python code

Code will be executed with Python 3 on the server

3. Contractile Apparatus

Smooth-muscle thin filaments anchor to cytoplasmic dense bodies (α-actinin) and membrane dense plaques rather than Z-discs. Myosin II filaments are shorter and irregularly-oriented. The absence of striation reflects this lack of sarcomeric organisation. The consequence: slower but more economic contraction, ~1% of skeletal ATP consumption for the same tension, and a much wider operating length range.

4. Phasic vs Tonic Smooth Muscle

Phasic smooth muscle (GI, ureter, oviduct) produces rhythmic contractions coordinated by slow-wave-generating interstitial cells of Cajal (ICC). Tonic smooth muscle (vascular, airway) maintains sustained tone. Asthma, hypertension, and IBS all reflect smooth-muscle dysregulation; therapeutic targets include β₂ agonists (albuterol, salbutamol), L-type Ca²⁺channel blockers (amlodipine, nifedipine), and guanylyl-cyclase stimulators.

Key References

• Somlyo, A. P. & Somlyo, A. V. (2003). “Ca²⁺ sensitivity of smooth muscle and nonmuscle myosin II.” Physiol. Rev., 83, 1325–1358.

• Webb, R. C. (2003). “Smooth muscle contraction and relaxation.” Adv. Physiol. Educ., 27, 201–206.

• Hirano, K. (2007). “Current topics in the regulatory mechanism underlying the Ca2+ sensitization of the contractile apparatus in vascular smooth muscle.” J. Pharmacol. Sci., 104, 109–115.

← 4.2 Cardiac 4.4 E-C Coupling →