Coordinate changes in fast thin filament and Z-line protein expression in the early response to chronic stimulation.

The early response to chronic low frequency stimulation is characterized by coordinate changes in fast thin filament and Z-line protein expression prior to the expression of slow contractile proteins. Within the first 3 weeks of intervention there is 1) a transition from expression of the fast troponin (Tn) Ts TnT1f and TnT2f to expression of TnT3f, 2) a parallel change in Z-line protein expression in which alpha-actinin1f/s becomes predominant, and 3) a small but significant increase in the levels of the beta-tropomyosin (Tm) subunit. The timing of these changes coincides with the conversion to thick Z-lines, and the kinetics of changes in fast TnT and alpha-actinin isoforms suggests that the expression of TnT3f with alpha-actinin1f/s and a combination of alpha beta and beta 2-Tm, which we have designated the TnT3f program, is coordinated. Because fast fibers expressing TnT3f with alpha beta and beta 2-Tm, like slow fibers, exhibit a more graded response to calcium (Schachat, F.H., Diamond, M.S., and Brandt, P.W. (1987) J. Mol. Biol., 198, 551-555), this change appears to be an adaptive response, illustrating the contribution of isoform diversity to the physiological plasticity of fast skeletal muscle and indicating that expression of the TnT3f program may be an intermediate phase in the conversion from a fast to a slow molecular phenotype.

Duke Scholars

Author Frederick Schachat Cell Biology

Author Robert Sanders Williams Medicine, Cardiology