The molecular basis for diminished muscle function in acidosis: a proposal.
1Newbridge on the Charles, Dedham, MA, 02026, USA. Sherwin.lehrer@gmail.com.
Journal of Muscle Research and Cell Motility
|February 13, 2020
Summary
Acidosis inhibits muscle contraction by altering calcium binding sites, leading to a blocked substate that prevents myosin interaction. This molecular proposal explains the effects of low pH on skeletal and cardiac muscle function.
Area of Science:
- Biochemistry
- Molecular Biology
- Muscle Physiology
Background:
- Presents a molecular hypothesis for acidosis effects on skeletal and cardiac muscle.
- Leverages 1974 fluorescence studies on EF-hand Ca2+ binding sites with abnormal pKa.
Discussion:
- Acidosis induces an H+-bound blocked substate within the 3-state muscle regulation model.
- This substate inhibits myosin binding in the physiological pH range of 7 to 6.
Key Insights:
- Carboxylate groups in Ca2+ binding sites exhibit altered pKa under acidic conditions.
- A novel blocked substate is proposed to mediate pH-dependent inhibition of muscle contraction.
Outlook:
- Further experimental validation of the proposed molecular mechanism.
- Potential therapeutic targets for muscle dysfunction associated with acidosis.
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