RT Journal Article
SR Electronic
T1 Myosin-binding protein C corrects an intrinsic inhomogeneity in cardiac excitation-contraction coupling
JF Science Advances
JO Sci Adv
FD American Association for the Advancement of Science
SP e1400205
DO 10.1126/sciadv.1400205
VO 1
IS 1
A1 Previs, Michael J.
A1 Prosser, Benjamin L.
A1 Mun, Ji Young
A1 Previs, Samantha Beck
A1 Gulick, James
A1 Lee, Kyounghwan
A1 Robbins, Jeffrey
A1 Craig, Roger
A1 Lederer, W. J.
A1 Warshaw, David M.
YR 2015
UL http://advances.sciencemag.org/content/1/1/e1400205.abstract
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.