In smooth muscle, excitation-contraction coupling involves calcium binding to which molecule, leading to activation of MLCK and phosphorylation of myosin heads?

• A. Calcium binds to troponin C to activate contraction.
• B. Calcium binds directly to actin to initiate contraction.
• C. Contraction occurs without calcium involvement.
• D. Calcium binds to calmodulin, activating myosin light-chain kinase, which phosphorylates myosin heads to interact with actin.

Answer: (D)

In smooth muscle, calcium regulates contraction through a calmodulin-dependent pathway. When calcium rises, it binds to calmodulin to form a calcium-calmodulin complex. This complex activates myosin light-chain kinase (MLCK). Activated MLCK then phosphorylates the regulatory light chains on myosin heads, increasing myosin ATPase activity and allowing cross-bridge cycling with actin to generate contraction. This mechanism contrasts with skeletal muscle, where calcium binds to troponin C to move tropomyosin away from actin’s binding sites. Calcium binding directly to actin or contraction without calcium aren’t the regulatory routes in smooth muscle, making the calmodulin-MLCK phosphorylation pathway the correct explanation. Relaxation occurs when myosin light-chain phosphatase dephosphorylates myosin, reversing the effect.