Research ArticleBIOPHYSICS

Myosin-binding protein C corrects an intrinsic inhomogeneity in cardiac excitation-contraction coupling

Science Advances  20 Feb 2015:
Vol. 1, no. 1, e1400205
DOI: 10.1126/sciadv.1400205

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Abstract

The beating heart exhibits remarkable contractile fidelity over a lifetime, which reflects the tight coupling of electrical, chemical, and mechanical elements within the sarcomere, the elementary contractile unit. On a beat-to-beat basis, calcium is released from the ends of the sarcomere and must diffuse toward the sarcomere center to fully activate the myosin- and actin-based contractile proteins. The resultant spatial and temporal gradient in free calcium across the sarcomere should lead to nonuniform and inefficient activation of contraction. We show that myosin-binding protein C (MyBP-C), through its positioning on the myosin thick filaments, corrects this nonuniformity in calcium activation by exquisitely sensitizing the contractile apparatus to calcium in a manner that precisely counterbalances the calcium gradient. Thus, the presence and correct localization of MyBP-C within the sarcomere is critically important for normal cardiac function, and any disturbance of MyBP-C localization or function will contribute to the consequent cardiac pathologies.

Keywords
  • myosin-binding protein C
  • native thick filaments
  • native thin filaments
  • calcium dynamics
  • phosphorylation
  • muscle activation
  • muscle regulation
  • cardiac excitation-contraction coupling

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