Smooth vs Cardiac vs Skeletal Muscle

Skeletal muscle — DHPR mechanically gates RyR1; it can twitch briefly in a calcium-free bath. Cardiac and smooth muscle both depend on Ca²⁺ entry from outside.

In cardiac muscle, Ca²⁺ entering through L-type channels during the plateau (phase 2) binds RyR2 on the SR, triggering a much larger SR calcium release (~25% extracellular, ~75% SR).

Calmodulin — smooth muscle has NO troponin. Ca²⁺–calmodulin activates MLCK, which phosphorylates the myosin regulatory light chain.

Thick filament (myosin) regulation via light-chain phosphorylation; skeletal and cardiac use thin-filament (actin) regulation via troponin/tropomyosin.

Dephosphorylates the myosin regulatory light chain, causing relaxation. Its inhibition by RhoA/Rho-kinase produces calcium sensitization — more force at the same [Ca²⁺].

The long plateau makes the absolute refractory period last nearly the whole contraction, so twitches cannot summate — essential for a pump.

β₁ → Gs → cAMP → PKA phosphorylates L-type Ca²⁺ channels (more entry), phospholamban (disinhibits SERCA, loads SR) and troponin I (faster relaxation = lusitropy).

Inhibits Na⁺/K⁺-ATPase → intracellular Na⁺ rises → Na⁺/Ca²⁺ exchanger (NCX) slows → SR calcium loading increases → stronger contraction.

Cross-bridges dephosphorylate while still attached and cycle extremely slowly, holding tension for hours at low ATP cost (e.g. arteriolar tone, sphincters).

Vascular smooth muscle depends on L-type channel Ca²⁺ entry and has a sparse SR, whereas skeletal muscle contraction needs no extracellular calcium.

Agonist → Gq → phospholipase C → IP₃ → IP₃ receptors on the SR release Ca²⁺; RyR-mediated CICR plays a smaller role.

It is a functional syncytium — gap junctions in intercalated discs spread current cell-to-cell; there is no motor unit recruitment.