PT  - JOURNAL ARTICLE
AU  - Previs, Michael J.
AU  - Prosser, Benjamin L.
AU  - Mun, Ji Young
AU  - Previs, Samantha Beck
AU  - Gulick, James
AU  - Lee, Kyounghwan
AU  - Robbins, Jeffrey
AU  - Craig, Roger
AU  - Lederer, W. J.
AU  - Warshaw, David M.
TI  - Myosin-binding protein C corrects an intrinsic inhomogeneity in cardiac excitation-contraction coupling
AID  - 10.1126/sciadv.1400205
DP  - 2015 Feb 01
TA  - Science Advances
PG  - e1400205
VI  - 1
IP  - 1
4099  - http://advances.sciencemag.org/content/1/1/e1400205.short
4100  - http://advances.sciencemag.org/content/1/1/e1400205.full
SO  - Sci Adv2015 Feb 01; 1
AB  - 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.