Role of intracellular Cd2+ in catecholamine release and lethality in PC12 cells.

To evaluate the role of intracellular Cd2+ in catecholamine release and lethality in rat pheochromocytoma (PC12) cells the following results were obtained: [1] the presence of Cd2+ intracellularly was demonstrated with the Cd(2+)-sensitive fluorescent dye BTC-5N, [2] Cd2+ entry through Ca(2+)-channels was either blocked with nifedipine or diltiazem or increased with Bay K8644, [3] Cd2+ entry through voltage sensitive Ca2+ channels was related to dopamine release and cell lethality, [4] a calmodulin inhibitor protected against Cd2+ toxicity, and [5] extracellular Ca2+ concentration, altered prior to Cd2+ exposure, was inversely related to dopamine release by Cd2+. The data indicate intracellular effects of Cd2+ rather than cell surface actions are primarily involved in neurotransmitter release and lethality by toxic levels of Cd2+ in adrenomedullary cells. To evaluate the role of intracellular Cd2+ in catecholamine release and lethality in rat pheochromocytoma (PC12) cells the following results were obtained: [1] the presence of Cd2+ intracellularly was demonstrated with the Cd(2+)-sensitive fluorescent dye BTC-5N, [2] Cd2+ entry through Ca(2+)-channels was either blocked with nifedipine or diltiazem or increased with Bay K8644, [3] Cd2+ entry through voltage sensitive Ca2+ channels was related to dopamine release and cell lethality, [4] a calmodulin inhibitor protected against Cd2+ toxicity, and [5] extracellular Ca2+ concentration, altered prior to Cd2+ exposure, was inversely related to dopamine release by Cd2+. The data indicate intracellular effects of Cd2+ rather than cell surface actions are primarily involved in neurotransmitter release and lethality by toxic levels of Cd2+ in adrenomedullary cells.