Effect of denervation on ATP consumption rate of diaphragm muscle fibers

Open Access
Publisher Website
Google Scholar
Abstract
Denervation (DNV) of rat diaphragm muscle (DIAm) decreases myosin heavy chain (MHC) content in fibers expressing MHC2Xisoform but not in fibers expressing MHCslowand MHC2A. Since MHC is the site of ATP hydrolysis during muscle contraction, we hypothesized that ATP consumption rate during maximum isometric activation (ATPiso) is reduced following unilateral DIAm DNV and that this effect is most pronounced in fibers expressing MHC2X. In single-type-identified, permeabilized DIAm fibers, ATPisowas measured using NADH-linked fluorometry. The maximum velocity of the actomyosin ATPase reaction ( VmaxATPase) was determined using quantitative histochemistry. The effect of DNV on maximum unloaded shortening velocity ( Vo) and cross-bridge cycling rate [estimated from the rate constant for force redevelopment ( kTR) following quick release and restretch] was also examined. Two weeks after DNV, ATPisowas significantly reduced in fibers expressing MHC2X, but unaffected in fibers expressing MHCslowand MHC2A. This effect of DNV on fibers expressing MHC2Xpersisted even after normalization for DNV-induced reduction in MHC content. With DNV, Voand kTRwere slowed in fibers expressing MHC2X, consistent with the effect on ATPiso. The difference between VmaxATPase and ATPisoreflects reserve capacity for ATP consumption, which was reduced across all fibers following DNV; however, this effect was most pronounced in fibers expressing MHC2X. DNV-induced reductions in ATPisoand VmaxATPase of fibers expressing MHC2Xreflect the underlying decrease in MHC content, while reduction in ATPisoalso reflects a slowing of cross-bridge cycling rate.