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Myosin binding protein-H like (MyBP-HL) has recently been identified as a novel component of myofilaments in the cardiac atria. Loss of MyBP-HL is associated with dilated cardiomyopathy and arrhythmia in humans and mice. MyBP-HL is highly homologous to cardiac myosin binding protein-C (cMyBP-C), which has been studied in the context of genetic cardiomyopathy. Prior work using mouse atrial tissue lysates established MyBP-HL and cMyBP-C bind competitively and maintain a stoichiometric ratio compared to myosin heavy chain. We now confirm this competitive binding using neonatal rat ventricular cardiomyocytes (NRVMs) transfected with mouse Mybphl . Using confocal microscopy with internal controls, we found a linear, inverse relationshib between myosin binding protein levels with NRVMs with high levels of MyBP-HL expression showing a reduction in cMyBP-C levels compared to untransfected NRVMs that only express cMyBP-C. While we show that these two myosin binding proteins bind comparatively with each other, the functional consequences are unclear. We performed force-calcium measurements of permeabilized single atrial cardiomyocytes and found that loss of MyBP-HL does not significantly alter the calcium sensitivity of force development, or the specific force generated by isometric contraction. Because cMyBP-C is a known regulator of crossbridge sliding velocity, we evaluated contraction and relaxation kinetics of Mybphl single-myofibrils from WT and Mybphl homozygous null mice. Atrial myofibrils lacking Mybphl showed a significantly faster rate and shorter duration of their linear phase of relaxation, which is governed by the off-rate of myosin from actin. This suggests that extra cMyBP-C in the atria can hasten myofibril relaxation. In healthy atria with MyBP-HL replacing approximately half the cMyBP-C, the slow phase of relaxation is prolonged. While the physiological importance of this is not explored, it provides a mechanism by which loss of function mutations in MYBPHL cause contractile dysfunction.

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