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Physostigmine-induced contractures in frog skeletal muscle
Pflugers Archiv : European Journal of Physiology
|June 22, 1976
Summary
Physostigmine induces reversible muscle contractures by releasing calcium from the sarcoplasmic reticulum, independent of external calcium or membrane depolarization. This action differs from caffeine
Area of Science:
- Muscle physiology
- Pharmacology
Background:
- Physostigmine is a reversible acetylcholinesterase inhibitor.
- Calcium ions play a crucial role in muscle contraction.
Purpose of the Study:
- To investigate the mechanism by which physostigmine induces muscle contractures.
- To compare the action of physostigmine with that of caffeine on muscle contraction.
Main Methods:
- Frog toe muscles and fiber bundles were used to measure tension output.
- Contractures were induced using various concentrations of physostigmine at different pH levels.
- Experiments included varying external calcium, membrane potential, and temperature, as well as glycerol treatment and procaine pretreatment.
Main Results:
- Physostigmine (15 mM) at pH 8.4 produced reversible contractures (up to 0.3 Po), significantly reduced at pH 7.2 (0.10 Po).
- Contractures were unaffected by calcium removal, depolarization, detubulation, or cold temperature.
- Procaine pretreatment reduced physostigmine-induced contractures, suggesting competitive inhibition at sarcoplasmic reticulum sites.
Conclusions:
- Physostigmine induces contracture by directly releasing calcium from the sarcoplasmic reticulum.
- Unlike caffeine, physostigmine-induced contractures are reversible and do not sensitize muscles to cooling.
- Physostigmine's internal action likely involves both charged and uncharged forms due to its weak base properties and intracellular pH.