Cadmium: effects on transmitter release at the frog neuromuscular junction

Cd2+ competitively antagonizes Ca2+ in the evoked release of acetylcholine from nerve terminals in the frog sciatic-sartorius neuromuscular junction. The dissociation constant between Cd2+ and its receptor sites was calculated to be 1.7 microM. In agreement with previous work we found that brief exposures to 100-500 microM Cd2+ had little or no effect on spontaneous transmitter release. However, in contrast to other reports, prolonged exposures to 100-100 microM Cd2+ or tetanic nerve stimulation during brief exposures to high concentrations of Cd2+ produced substantial increases in spontaneous transmitter release. We conclude that Cd2+, when present at low concentrations, is a specific Ca2+ channel blocker. At higher concentrations, Cd2+ is either relatively impermeable to the presynaptic nerve membrane or, if it does enter the nerve terminal, it is less effective than such metals as Pb2+, La3+ or Hg2+ in increasing the rate of spontaneous transmitter release.