The contribution of postsynaptic folds to the safety factor for neuromuscular transmission in rat fast- and slow-twitch muscles

1. At the rat neuromuscular junction, the postsynaptic folds and the voltage-gated sodium channels (VGSCs) within them are thought to amplify the effects of postsynaptic currents. In this study, the contribution of this effect to the safety factor for neuromuscular transmission, the ratio of the normal quantal content to the number of quanta required to reach threshold, has been estimated. 2. Normal quantal content was determined in isolated nerve-muscle preparations of rat soleus and extensor digitorum longus (EDL) muscles in which muscle action potentials were blocked by mu-conotoxin. The quantal content estimated from voltage recordings was 61.8 and 79.4 in soleus and EDL, respectively, and from charge measurements derived from current recordings was 46.3 (soleus) and 65.1 (EDL). 3. The threshold for action potential generation in response to nerve stimulation was determined from endplate potentials (EPPs) and endplate currents (EPCs) in preparations partially blocked with d-tubocurarine. The number of quanta required to reach threshold was estimated from voltage recordings to be 19.7 (soleus) and 23.2 (EDL) and from charge measurements derived from current recordings to be 13.3 (soleus) and 13.0 (EDL). 4. When intracellular electrodes were used to inject current into the muscle fibre, the total charge required to reach threshold was approximately twice that of the nerve-evoked threshold (EPC). 5. The safety factor for nerve-evoked responses at the junction was 3.5 (soleus) and 5.0 (EDL). In the extrajunctional region the safety factor estimated from injected currents was 1.7 (soleus) and 2.5 (EDL). 6. It is concluded that the effect of the postsynaptic folds and the VGSCs within them is to double the safety factor. At normal frequencies of nerve impulse activity in vivo, this effect is likely to be crucial far ensuring effective neuromuscular transmission.