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Inhibitory action of high formamide concentrations on excitation-contraction coupling in skeletal muscle
Abstract:
Strips of guinea pig ileum lose over 70% of their contractility when bathed in Krebs-Ringer solution containing 0.4-0.9 M formamide (FMD). This effect is not accompanied by an appreciable loss of tissue water and is totally reversed by washing the preparation in normal solution. Frog sartorius muscles also paralyze when immersed in Ringer containing FMD, but higher concentrations (1.0-2.0 M) and longer exposure times are required. Contractility is not recovered upon transferring these muscles to normal Ringer. However, the contractile proteins still respond to activator calcium as shown by the fact that these muscles still contract in the presence of caffeine. The membrane of muscles uncoupled by FMD retain electrical excitability, and neuromuscular transmission appears to be unimpaired. However, alterations in the early after-potential of the spikes suggest the occurrence of a sarcotubular disruption. Therefore, FMD appears to exert two separate effects on muscle: a reversible inhibition of contractility, as observed in ileal strips and an irreversible blockade due to an osmotic shock observed when frog muscles are returned to normal Ringer. The reversible effect is probably related to interference with the availability of activator calcium, since no marked inhibitory effects on the activities of the actomyosin-like and the calcium-dependent and -independent ATPases could be observed on FMD-treated subcellular fractions.
Insights
Formamide (FMD) reversibly inhibits muscle contractility by affecting calcium availability in guinea pig ileum. In frog muscles, FMD causes irreversible blockade due to osmotic shock, highlighting dual effects on muscle function.
Area of Science:
- Muscle Physiology
- Pharmacology
Background:
- Formamide (FMD) is known to affect cellular functions.
- Understanding its specific impact on muscle contractility is crucial.
Purpose of the Study:
- To investigate the effects of formamide on muscle contractility in different species.
- To elucidate the mechanisms underlying formamide-induced muscle dysfunction.
Main Methods:
- Exposing guinea pig ileum strips and frog sartorius muscles to varying concentrations of formamide.
- Assessing contractility, tissue water content, and electrical excitability.
- Evaluating contractile protein response to calcium and caffeine.
Main Results:
- Formamide (0.4-0.9 M) reversibly inhibited guinea pig ileum contractility without significant water loss.
- Higher formamide concentrations (1.0-2.0 M) irreversibly blocked frog muscle contractility, suggesting osmotic shock.
- Muscle membranes retained electrical excitability, and neuromuscular transmission was unimpaired, but sarcotubular disruption was indicated.
Conclusions:
- Formamide exhibits dual effects: reversible inhibition of contractility possibly via calcium interference and irreversible blockade from osmotic shock.
- The reversible effect in ileum strips may involve altered activator calcium availability.
- The irreversible effect in frog muscles is linked to osmotic shock upon return to normal Ringer solution.