Mechanisms of the neuromuscular blocking activity of the aminoglycoside antibiotic streptomycin.

While increasing the spontaneous quantal transmitter release in frog neuromuscular junctions, streptomycin blocked the evoked transmitter release by decreasing the quantal content (m). The quantal parameter of release n (number of release sites) was significantly decreased, while p (probability of release through transmitter activation) increased. Streptomycin competes with calcium ions for the membrane release sites while the intracellular mechanisms of release remain unaffected. The data show a good fit to the two-step hypothesis of quantal transmitter release recently developed on the basis of ouabain actions.

Adenosine effects upon transmitter release parameters in the Mg2+-paralyzed neuro-muscular junction of frog.

The influence of adenosine upon the process of transmitter release was investigated in Mg2+-paralyzed frog neuromuscular junction by using conventional microelectrophysiological techniques and binomial statistical analysis. The statistical parameters used were: m (mean number of quanta released per impulse), p (the probability of quantal release) and n (store of quanta available for release). Adenosine decreased the mean quantal content (m) by reducing n. This effect appeared to be dependent upon the free intracellular Ca2+. The nucleoside competed with the transmitter releasing effects of ouabain and increased the amount of effective Ca2+ necessary for quantal release. It did not change the slope of release parameters modification during low-frequency facilitation. The data are discussed in terms of a physical model of release.

Dual action of ouabain on transmitter release at neuromuscular junctions of the frog.

Ouabain increased both spontaneous and evoked transmitter release in Mg++-treated frog neuromuscular junctions. This action developed as a two-step process which affected both miniature end-plate potential (m.e.p.p.) frequency and the binomial distribution of e.p.p.s. During the first part of its action, which lasts for approximately 60 min, ouabain (10(-5) M) increased the m.e.p.p. frequency following a saturable process. The increase in m.e.p.p. frequency was blocked by tetrodotoxin (15 nM). The quantal parameters of release, m and n, showed a significant increase but the parameter p was unaffected. Since the same changes in the binomial parameters were observed in Mg++-treated junctions exposed to low [Na+]0 in the absence of ouabain, it can be concluded that Na+ concentration played an important role in the increase of transmitter release. After 60 min in ouabain (10(-5) M) m.e.p.p. frequency increased by an exponential process. The binomial parameters of transmitter release, m and p, increased while n remained unchanged. This action was not influenced by TTX pretreatment nor was it reproduced by decreasing [Na+]0. The mechanism responsible for this action seems to be the Ca++- releasing effect of ouabain from the cytoplasmic sequestering sites.