Deletion of 1-43 amino acids in cardiac myosin essential light chain blunts length dependency of ca2+ sensitivity and cross-bridge detachment kinetics

John Jeshurun Michael, Sampath K. Gollapudi, Steven J. Ford, Katarzyna Kazmierczak, Danuta Szczesna-Cordary, Murali Chandra

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Abstract

The role of cardiac myosin essential light chain (ELC) in the sarcomere length (SL) dependency of myofilament contractility is unknown. Therefore, mechanical and dynamic contractile properties were measured at SL 1.9 and 2.2 m in cardiac muscle fibers from two groups of transgenic (Tg) mice: 1) Tg-wild-type (WT) mice that expressed WT human ventricular ELC and 2) Tg-Δ43 mice that expressed a mutant ELC lacking 1-Δ43 amino acids. In agreement with previous studies, Ca2+-activated maximal tension decreased significantly in Tg-Δ43 fibers. pCa50 (-log10 [Ca2+]free required for half maximal activation) values at SL of 1.9 m were 5.64Δ0.02 and 5.70±0.02 in Tg-Δ43 and Tg-Δ43 fibers, respectively. pCa50 values at SL of 2.2μm were 5.70Δ0.01 and 5.71±0.01 in Tg-Δ43 and Tg-δ43 fibers, respectively. The SLmediated increase in the pCa50 value was statistically significant only in Tg-Δ43 fibers (P<0.01), indicating that the SL dependency of myofilament Ca2+ sensitivity was blunted in Tg-43 fibers. The SL dependency of cross-bridge (XB) detachment kinetics was also blunted in Tg-Δ43 fibers because the decrease in XB detachment kinetics was significant (P<0.001) only at SL 1.9μm. Thus the increased XB dwell time at the short SL augments Ca2+ sensitivity at short SL and thus blunts SL-mediated increase in myofilament Ca2+ sensitivity. Our data suggest that the NH2-terminal extension of cardiac ELC not only augments the amplitude of force generation, but it also may play a role in mediating the SL dependency of XB detachment kinetics and myofilament Ca2+ sensitivity.

Original languageEnglish (US)
Pages (from-to)H253-H259
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume304
Issue number2
DOIs
StatePublished - Jan 15 2013

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Keywords

  • Cross-bridge detachment rate
  • Length-dependent activation of the myofilament
  • Maximal tension

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

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