Spontaneous and evoked synaptic transmission were studied at the rat extensor digitorum longus (EDL) neuromuscular junction in the presence of CGIIIA mu-conotoxin, a peptide which suppresses action potential in the sarcolemma, while not affecting impulse conduction along motor nerve fibers. The binomial parameters m (mean quantal content) and n (number of units involved in evoked quantal release) increased as a function of extracellular Ca++ ([Ca++]o), up to the physiological concentration (2 mM). Additional Ca++ failed to induce a statistically significant increase in either m or n, while the probability of activation (p) did increase, approaching unity at 4 mM [Ca++]o. In cut EDL preparations, without CGIIIA, the relation between end-plate potential amplitude and [Ca++]o resembled that for quantal content in unlesioned, CGIIIA-treated muscles. In contrast, normal preparations exposed to 0.5 mg/ml d-tubocurarine were much more responsive to Ca++ variations, with a significant end-plate potential amplitude increase in the presence of 4 mM [Ca++]o. However, in curarized preparation the evoked release was remarkably affected by repetitive stimulation, while in the absence of postsynaptic blockers release levels were more stable. We suggest that the stimulatory effect of extracellular Ca++ on evoked release at the mammalian neuromuscular junction might normally be depressed under physiological conditions, possibly by a down-regulation mechanism involving presynaptic nicotinic receptors. Such inhibition would increase nerve transmission efficiency during prolonged motor terminal activity.

A nerve guide made of a benzyl ester of hyaluronic acid (HYAFF11p75) was used to bridge 8 mm gaps in rat tibial nerves. Histologic observations indicated that this biomaterial provoked only a transient, modest inflammatory response, and the resorption rate was compatible with the nerve regeneration processes. Phagocytosis of the biomaterial began after neoangiogenesis and cell migration had taken place from both stumps into the nerve guide material. For comparison, the regeneration achieved was evaluated in nerve guides made of either HYAFF11p75 or Silastic, and in nerves repaired with the autograft technique. Recovery was assessed in vivo 90 days after implantation by measuring the nerve compound action potential (CAP) and conduction velocity (NCV) of the regenerated tibial nerve. The results demonstrate that the nerve guide tubes made of HYAFF11p75 were able to support and direct axonal growth, thereby suggesting a possible use for such biomaterial in the management of short nerve gaps in human pathology.

Quantal acetylcholine release was studied in sciatic nerve — extensor digitorum longus muscle preparations from normal rats and in reinnervated muscles at different times following peroneus nerve crush. The efficiency of nerve-evoked transmission was regained almost completely at a time (20 days after crush) when the secretory response to increased extracellular K+ was very weak. This suggests that K+-induced secretion might be activated through mechanisms at least partially different from those involved in the response to nerve stimulation.