Smooth muscle contraction differs from skeletal muscle because it uses a calmodulin-MLCK pathway rather than troponin-tropomyosin. A patient receiving a calcium channel blocker for hypertension shows reduced vascular tone. Which molecular step is directly inhibited by reducing intracellular Ca²⁺ in vascular smooth muscle?

• A Reduced Ca²⁺ decreases Ca²⁺-calmodulin complex formation; without Ca²⁺-CaM, myosin light chain kinase (MLCK) remains inactive; MLC remains unphosphorylated; myosin cannot interact with actin; no contraction occurs ✓
• B Reduced Ca²⁺ blocks the troponin C binding site, preventing troponin I inhibition of actin, similar to skeletal muscle
• C Reduced Ca²⁺ activates myosin light chain phosphatase (MLCP), which continuously dephosphorylates MLC, and the CCB enhances this activation
• D Reduced Ca²⁺ opens ATP-sensitive K⁺ channels (KATP) in the smooth muscle membrane, causing hyperpolarisation that indirectly reduces MLCK activity

Explanation

Vascular smooth muscle contraction requires: Ca²⁺ enters via L-type voltage-gated Ca²⁺ channels → binds calmodulin (4 Ca²⁺ per CaM) → Ca²⁺-CaM complex activates MLCK → MLCK phosphorylates MLC₂₀ at Ser19 → phospho-MLC₂₀ increases actin-activated myosin ATPase activity → cross-bridge cycling and contraction. CCBs block L-type channels, reducing Ca²⁺ influx and thus Ca²⁺-CaM available to activate MLCK; unphosphorylated MLC means no contraction, producing vasodilation and BP reduction. Smooth muscle lacks troponin (option B is incorrect). MLCP is constitutively active and not specifically activated by low Ca²⁺ in the way described in option C — Rho-kinase inhibits MLCP under contractile stimuli. KATP channels mediate some vascular relaxation but are not the primary mechanism of CCB action.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

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