Document Detail

The effects of phosphate and acidosis on regulated thin-filament velocity in an in vitro motility assay.
MedLine Citation:
PMID:  23019317     Owner:  NLM     Status:  MEDLINE    
Muscle fatigue from intense contractile activity is thought to result, in large part, from the accumulation of inorganic phosphate (P(i)) and hydrogen ions (H(+)) acting to directly inhibit the function of the contractile proteins; however, the molecular basis of this process remain unclear. We used an in vitro motility assay and determined the effects of elevated H(+) and P(i) on the ability of myosin to bind to and translocate regulated actin filaments (RTF) to gain novel insights into the molecular basis of fatigue. At saturating Ca(++), acidosis depressed regulated filament velocity (V(RTF)) by ≈ 90% (6.2 ± 0.3 vs. 0.5 ± 0.2 μm/s at pH 7.4 and 6.5, respectively). However, the addition of 30 mM P(i) caused V(RTF) to increase fivefold, from 0.5 ± 0.2 to 2.6 ± 0.3 μm/s at pH 6.5. Similarly, at all subsaturating Ca(++) levels, acidosis slowed V(RTF), but the addition of P(i) significantly attenuated this effect. We also manipulated the [ADP] in addition to the [P(i)] to probe which specific step(s) of cross-bridge cycle of myosin is affected by elevated H(+). The findings are consistent with acidosis slowing the isomerization step between two actomyosin ADP-bound states. Because the state before this isomerization is most vulnerable to P(i) rebinding, and the associated detachment from actin, this finding may also explain the P(i)-induced enhancement of V(RTF) at low pH. These results therefore may provide a molecular basis for a significant portion of the loss of shortening velocity and possibly muscular power during fatigue.
Edward P Debold; Thomas J Longyear; Matthew A Turner
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-09-27
Journal Detail:
Title:  Journal of applied physiology (Bethesda, Md. : 1985)     Volume:  113     ISSN:  1522-1601     ISO Abbreviation:  J. Appl. Physiol.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-05     Completed Date:  2013-04-12     Revised Date:  2013-09-26    
Medline Journal Info:
Nlm Unique ID:  8502536     Medline TA:  J Appl Physiol (1985)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1413-22     Citation Subset:  IM    
Department of Kinesiology, University of Massachusetts, Amherst, Massachusetts 01003, USA.
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MeSH Terms
Acidosis / physiopathology
Actin Cytoskeleton / physiology*
Calcium / metabolism
Hydrogen-Ion Concentration
Models, Biological
Muscle Contraction / physiology*
Muscle Fatigue / physiology
Myosins / physiology*
Phosphates / metabolism
Protein Binding
Tropomyosin / physiology
Troponin / physiology
Reg. No./Substance:
0/Phosphates; 0/Tropomyosin; 0/Troponin; 7440-70-2/Calcium; EC

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