Phosphorylation of the regulatory light chains of myosin affects Ca2+ sensitivity of skeletal muscle contraction

Danuta Szczesna, Jiaju Zhao, Michelle Jones, Gang Zhi, James Stull, James D. Potter

Research output: Contribution to journalArticlepeer-review

88 Scopus citations


The role of phosphorylation of the myosin regulatory light chains (RLC) is well established in smooth muscle contraction, but in striated (skeletal and cardiac) muscle its role is still controversial. We have studied the effects of RLC phosphorylation in reconstituted myosin and in skinned skeletal muscle fibers where Ca2+ sensitivity and the kinetics of steady-state force development were measured. Skeletal muscle myosin reconstituted with phosphorylated RLC produced a much higher Ca2+ sensitivity of thin filament-regulated ATPase activity than nonphosphorylated RLC (change in -log of the Ca2+ concentration producing half-maximal activation = ∼0.25). The same was true for the Ca2+ sensitivity of force in skinned skeletal muscle fibers, which increased on reconstitution of the fibers with the phosphorylated RLC. In addition, we have shown that the level of endogenous RLC phosphorylation is a crucial determinant of the Ca2+ sensitivity of force development. Studies of the effects of RLC phosphorylation on the kinetics of force activation with the caged Ca2+, DM-nitrophen, showed a slight increase in the rates of force development with low statistical significance. However, an increase from 69 to 84% of the initial steady-state force was observed when nonphosphorylated RLC-reconstituted fibers were subsequently phosphorylated with exogenous myosin light chain kinase. In conclusion, our results suggest that, although Ca2+ binding to the troponin-tropomyosin complex is the primary regulator of skeletal muscle contraction, RLC play an important modulatory role in this process.

Original languageEnglish (US)
Pages (from-to)1661-1670
Number of pages10
JournalJournal of applied physiology
Issue number4
StatePublished - 2002


  • Calcium regulation
  • Myosin light chain kinase
  • Regulatory light chain depletion
  • Steady-state force

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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