title: Multiple actions of cadmium on transmitter release at the mouse neuromuscular junction.
abstract: The action of cadmium ions on transmitter release was studied at the neuromuscular junction in mouse diaphragm. In the presence of raised K+, Cd2+ caused a parallel shift to the right of the graph of transmitter release rate (frequency of miniature end-plate potentials, fmepp) versus log [Ca2+], with no change in maximum or slope, indicating a competitive mode of action of Cd2+. The apparent dissociation constant for Cd2+ was 3 microM. In calcium-free solutions containing 15 mM K+, Cd2+ caused a rise in the fmepp, which subsequently slowly declined despite the continued presence of Cd2+. The rise in fmepp caused by Cd2+ could be interrupted, but not reversed, by washing out the Cd2+ with EDTA. Exposure of the preparation to 100 microM Cd2+ for 15 min or more resulted in a raised fmepp that persisted despite the removal of Cd2+ and exposure to 200 microM EDTA. Following such treatment, the graph of fmepp versus log [Ca2+] continued to be shifted to the right. The interaction of Ca2+ with the residual effect of Cd2+ indicates that Cd2+, in addition to its action to block Ca2+ entry into the terminal, may act as a competitor and perhaps as a partial agonist at intracellular sites that normally bind Ca2+ and govern transmitter release. If this is the case, then it must be supposed that, in raised K+, quantal release of transmitter represents intermittent intense activation of release sites with local high levels of Ca2+ rather than continuous low level activation.
mesh_terms: D000465:Algorithms; D000818:Animals; D002104:Cadmium / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004492:Edetic Acid / Q000494:pharmacology; D051379:Mice; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism
chemical_list: D018377:Neurotransmitter Agents; D002104:Cadmium; D004492:Edetic Acid; D011188:Potassium; D002118:Calcium