Lanthanum as a surrogate for calcium in transmitter release at mouse motor nerve terminals.

The mechanism by which lanthanum (La3+) causes an increased frequency of miniature end-plate potentials (m.e.p.p.s) was studied at the mouse neuromuscular junction. At concentrations as low as 0.25 microM, La3+ caused a progressive rise in m.e.p.p. frequency, to a maximum of several hundred per second. 'Washing' with solution containing EDTA arrested the rise, but did not substantially reduce the raised m.e.p.p. frequency. At partially 'lanthanized' junctions high frequencies of m.e.p.p.s were maintained indefinitely, even in 0 Ca2+/EDTA solutions. The rate of development of high m.e.p.p. frequency was increased by repetitive nerve stimulation or by depolarization of the nerve terminal (high K+ or focally applied current), and appeared to be proportional to the concentration of La3+ over the range of 0.25-5 microM. At low concentrations of La3+ the rise of m.e.p.p. frequency depended upon the co-presence of a small amount of Ca2+ (greater than 10 microM) and was slowed and partially blocked by Cd2+, or by Ca2+ at about 10 microM. The quantal content of end-plate potentials was usually reduced in the presence of La3+, but was increased over control values after removal of La3+ by 'washing' with solution containing EDTA, once a raised m.e.p.p. frequency had developed. At partially lanthanized junctions the absolute increases in m.e.p.p. frequency produced by Ca2+ (in raised K+), ethanol, or by nerve stimulation in the presence of Ba2+, were greater than at control junctions, but in each case the increases in the logarithm of m.e.p.p. frequency were less than at control junctions. It is concluded that La3+ causes transmitter release only after entry into the nerve terminal via voltage-sensitive channels, probably those that normally admit Ca2+, that La3+ and Ca2+ may co-operate at internal sites to induce transmitter release, and that these ions both co-operate and compete at external sites that regulate their entry into the nerve terminal.