Myosin-binding protein C corrects an intrinsic inhomogeneity in cardiac excitation-contraction coupling
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
+ Author Affiliations
Sci. Adv. 2015;1:e1400205 20 February 2015
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.