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


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.

Autor / Fonte:Michael J. Previs, Benjamin L. Prosser, Ji Young Mun, Samantha Beck Previs, James Gulick, Kyounghwan Lee, Jeffrey Robbins, Roger Craig, W. J. Lederer, David M. Warshaw. Science Advances 20 Feb 2015: Vol. 1 no. 1 e1400205 DOI: 10.1126/sciadv.1400205