Some effects of lead at mammalian neuromuscular junction.

The effect of lead on transmitter release was investigated in a rat phrenic nerve-hemidiaphragm preparation using conventional microelectrode techniques. Lead reduced the number of quanta released by a nerve stimulus (m) in a dose-dependent fashion. As extracellular Ca2+ concentration ([Ca2+]o) was varied in the absence of lead, a linear relationship between ln(m) and ln([Ca2+]o) was obtained. Lead shifted the relationship between ln(m) and ln([Ca2+]o) to the right without altering the slope. This suggested lead competed with Ca2+, which was confirmed by using a modified Lineweaver-Burk plot. Lead inhibits Ca2+ entry into frog sympathetic preganglionic nerve terminals, and a similar mechanism may underlie this present finding; such a mechanism, however, could not explain all the observed actions of lead. Lead increased the frequency of spontaneous quantal release in a dose-dependent manner, and 10(-4) M lead doubled the magnitude of facilitation of evoked release seen with five stimuli at 60 Hz. It is suggested that these effects result from inhibition of some, or all, of the nerve terminal's Ca2+ sequestration mechanisms.