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Effect of denervation on ATP consumption rate of diaphragm muscle fibers

Gary C Sieck1, Wen-Zhi Zhan, Young-Soo Han

  • 1Department of Physiology and Biomedical Engineering, Mayo Clinic and Foundation, 200 First St. SW, Rochester, MN 55905, USA. sieck.gary@mayo.edu

Journal of Applied Physiology (Bethesda, Md. : 1985)
|June 9, 2007
PubMed

Insights

Denervation reduces ATP consumption in rat diaphragm muscle fibers, particularly those with MHC(2X) isoforms. This ATP reduction is linked to decreased myosin heavy chain content and slower cross-bridge cycling.

Area of Science:

  • Muscle physiology
  • Biochemistry
  • Cellular biology

Background:

  • Denervation (DNV) of rat diaphragm muscle (DIAm) selectively reduces myosin heavy chain (MHC) content in MHC(2X) isoform-expressing fibers.
  • Myosin heavy chain (MHC) is crucial for ATP hydrolysis during muscle contraction.

Purpose of the Study:

  • To investigate the hypothesis that ATP consumption rate during maximum isometric activation (ATP(iso)) is reduced following unilateral DIAm DNV.
  • To determine if this reduction is most pronounced in MHC(2X) isoform-expressing fibers.

Main Methods:

  • Measured ATP(iso) in single-type-identified, permeabilized DIAm fibers using NADH-linked fluorometry.
  • Determined maximum velocity of actomyosin ATPase reaction (V(max) ATPase) via quantitative histochemistry.
  • Examined effects of DNV on maximum unloaded shortening velocity (V(o)) and cross-bridge cycling rate (k(TR)).

Main Results:

  • Two weeks post-DNV, ATP(iso) significantly decreased in MHC(2X) fibers, but not in MHC(slow) or MHC(2A) fibers.
  • This reduction in MHC(2X) fibers persisted even after normalizing for MHC content reduction.
  • V(o) and k(TR) were slowed in MHC(2X) fibers post-DNV, correlating with reduced ATP(iso).
  • Reserve ATP consumption capacity was reduced in all fiber types post-DNV, most notably in MHC(2X) fibers.

Conclusions:

  • DNV-induced reductions in ATP(iso) and V(max) ATPase in MHC(2X) fibers are attributed to decreased MHC content.
  • Reduced ATP(iso) also reflects a slower cross-bridge cycling rate following denervation.
  • These findings highlight the differential impact of denervation on muscle fiber types and their metabolic function.

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