Male but not female mice carrying a single R403Q missense allele for cardiac 
alpha-myosin heavy chain (M-alphaMHC(R403Q/+) and F-alphaMHC(R403Q/+), 
respectively) develop significant hypertrophic cardiomyopathy (HCM) compared 
with male and female wild-type mice (M-alphaMHC(+/+) and F-alphaMHC(+/+), 
respectively) after approximately 30 wk of age. We tested the hypothesis that 
myofilament mechanical performance differs between M-alphaMHC(R403Q/+) and 
F-alphaMHC(R403Q/+) at younger ages (10-20 wk) and could account for sex 
differences in HCM development. The sensitivity of chemically skinned myocardial 
strips to Ca(2+) activation (pCa(50)) was significantly (P < 0.05) enhanced in 
male mice independent of genotype (M-alphaMHC(R403Q/+): 5.70 +/- 0.06, 
M-alphaMHC(+/+): 5.63 +/- 0.05, F-alphaMHC(R403Q/+): 5.57 +/- 0.03, 
F-alphaMHC(+/+): 5.54 +/- 0.04) by two-way ANOVA, whereas maximum developed 
tension was significantly enhanced in alpha-MHC(R403Q/+) independent of sex 
(M-alphaMHC(R403Q/+): 29.3 +/- 2.3, M-alphaMHC(+/+): 26.0 +/- 1.4, 
F-alphaMHC(R403Q/+): 30.2 +/- 2.1, F-alphaMHC(+/+): 26.2 +/- 1.2 mN/mm(2)). The 
frequency of maximum work generated by sinusoidal length perturbation was 
significantly higher in alphaMHC(R403Q/+) mice than in sex-matched controls 
(M-alphaMHC(R403Q/+): 2.26 +/- 0.47, M-alphaMHC(+/+): 1.29 +/- 0.18, 
F-alphaMHC(R403Q/+): 3.21 +/- 0.33, F-alphaMHC(+/+): 2.52 +/- 0.36 Hz). Unloaded 
shortening velocity was significantly enhanced in alphaMHC(R403Q/+) and in 
female mice (M-alphaMHC(R403Q/+): 2.26 +/- 0.47, M-alphaMHC(+/+): 1.29 +/- 0.18, 
F-alphaMHC(R403Q/+): 3.21 +/- 0.33, F-alphaMHC(+/+): 2.52 +/- 0.36 muscle 
lengths/s), and normalized mechanical power, calculated from the 
tension-velocity relationship, was significantly enhanced in alphaMHC(R403Q/+) 
independent of sex (M-alphaMHC(R403Q/+): 60 +/- 2 10(-3), M-alphaMHC(+/+): 37 
+/- 3 10(-3), F-alphaMHC(R403Q/+): 57 +/- 3 10(-3), F-alphaMHC(+/+) 25 +/- 3 
10(-3) muscle lengths/s x normalized tension). We did not find a statistically 
significant sex x mutation interaction for any measure of myofilament 
performance. Therefore, sarcomeric incorporation of the R403Q myosin similarly 
enhanced left ventricular myofilament mechanical performance in both male and 
female mice. The sex-dependent development of HCM due to the R403Q myosin may 
then be inhibited by female sex hormones, which may additionally underlie the 
observed sex differences for pCa(50) and unloaded shortening velocity.