Binding of³H-labelled cobra neurotoxin to cholinergic receptors in fast and slow mammalian muscles

Summary

A cobra neurotoxin (Naja naja siamensis 3) acts by blocking acetylcholine receptors of mouse fast and slow muscles in an irreversible way.

³H-labelling of this neurotoxin does not seriously diminish its blocking potency. Its blocking effect on neuromuscular transmission in an isolated phrenic nerve-hemidiaphragm preparation is dependent upon incubation time and toxin concentration. Binding of the toxin to the extensor digitorum longus muscle of the mouse incubatedin vitro is a function of toxin concentration, incubation time and temperature. The binding is an “adsorption” to receptive sites. Longer incubation at +37°C gives a slow increase in binding which does not occur at +4°C. Decamethonium and carbachol, which are known to desensitize the acetylcholine receptor, reduce toxin binding. After denervation an increase in toxin binding per mg wet weight of muscle is observed with peak values at 6 and 21 days following denervation for the fast extensor digitorum longus muscle and the slow soleus muscle, respectively. The highest extrajunctional receptor density of extensor digitorum longus and soleus muscles after denervation was about 3–5× 10² μm⁻² respectively. The junctional receptor density of the extensor muscle was estimated at about 1–2×10⁴ μm−2.