Figure 8.

Mavacamten populates myosin in the SRX state equally well in healthy and diseased models. Comparison of the concentration-dependent effect of mavacamten between PcSTF-WT and PcSTF-R403Q for (A) A_slow and (B) k_fast. Comparison of the effect of mavacamten between BcSTFs made from α-cardiac and β-cardiac myosin for (C) A_slow and (D) k_fast. The nomenclature is as follows: PcSTFs and BcSTFs refer to porcine and bovine cardiac synthetic thick filaments, and BcSTFa and BcSTFv refer to bovine cardiac synthetic thick filaments made from left atrial (α-cardiac) and left ventricular (β-cardiac) full-length myosin, respectively. Data were expressed as the mean ± SEM (n ≥ 4 from two experiments). In panels A and B, the concentrations of mavacamten required for half-maximal change (EC₅₀) in A_slow for WT and R403Q PcSTFs were 1.76 ± 0.22 and 2.00 ± 0.28, whereas those (IC₅₀) for k_fast were 0.29 ± 0.02 and 0.30 ± 0.02 μM, respectively. Similarly, in panels C and D, the EC₅₀ of A_slow for BcSTFa and BcSTFv were 1.83 ± 0.25 and 1.03 ±0.11 μM, whereas IC₅₀ of k_fast were 0.61 ± 0.08 and 0.35 ± 0.06 μM, respectively. SRX, super-relaxed.