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Acidosis affects muscle contraction by slowing the rates myosin attaches to and detaches from actin.

Abstract：

:The loss of muscle force and power during fatigue from intense contractile activity is associated with, and likely caused by, elevated levels of phosphate ([Formula: see text]) and hydrogen ions (decreased pH). To understand how these deficits in muscle performance occur at the molecular level, we used direct measurements of mini-ensembles of myosin generating force in the laser trap assay at pH 7.4 and 6.5. The data are consistent with a mechanochemical model in which a decrease in pH reduces myosin's detachment from actin (by slowing ADP release), increases non-productive myosin binding (by detached myosin rebinding without a powerstroke), and reduces myosin's attachment to actin (by slowing the weak-to-strong binding transition). Additional support of this mechanism is found by incorporating it into a branched pathway model for the effects of [Formula: see text] on myosin's interaction with actin. Including pH-dependence in one additional parameter (acceleration of [Formula: see text]-induced detachment), the model reproduces experimental measurements at high and low pH, and variable [Formula: see text], from the single molecule to large ensemble levels. Furthermore, when scaled up, the model predicts force-velocity relationships that are consistent with muscle fiber measurements. The model suggests that reducing pH has two opposing effects, a decrease in attachment favoring a decrease in muscle force and a decrease in detachment favoring an increase in muscle force. Depending on experimental details, the addition of [Formula: see text] can strengthen one or the other effect, resulting in either synergistic or antagonistic effects. This detailed molecular description suggests a molecular basis for contractile failure during muscle fatigue.

journal_name

J Muscle Res Cell Motil

journal_title

Journal of muscle research and cell motility

authors

Jarvis K,Woodward M,Debold EP,Walcott S

doi

10.1007/s10974-018-9499-7

subject

Has Abstract

pub_date

2018-08-01 00:00:00

pages

135-147

issue

3-4

eissn

0142-4319

issn

1573-2657

pii

10.1007/s10974-018-9499-7

journal_volume

pub_type

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Acidosis affects muscle contraction by slowing the rates myosin attaches to and detaches from actin.