The role of intracellular calcium in antimony-induced toxicity in cultured cardiac myocytes.
Wey-HE; Richards-D; Tirmenstein-MA; Mathias-PI; Toraason-M
Toxicol Appl Pharmacol 1997 Jul; 145(1):202-210
Trivalent antimony, delivered as potassium antimonyl tartrate (PAT), has been previously shown to induce an oxidative stress and toxicity in cultured neonatal rat cardiac myocytes. The present study investigates the effect of PAT on intracellular free calcium ([Ca2+]i), which has been implicated in the toxicity of agents inducing oxidative stress, and explores its role in PAT toxicity. Exposure to 50 or 200 µ PAT led to progressive elevation in diastolic or resting [Ca2+]iand eventually a complete loss of [Ca2+]itransients that occurred well before cell death as assessed by LDH release. Prior loading of myocytes with the intracellular calcium chelator BAPTA (10 to 40 µ ), protected against PAT toxicity in the presence and absence of extracellular calcium, and demonstrated a crucial role for [Ca2+]iin PAT toxicity. Exposure to 200 µ PAT in the absence of extracellular calcium slightly elevated [Ca2+]i, but only to levels comparable to resting [Ca2+]ifor cells in 1.8 m extracellular calcium. This demonstrated that although PAT toxicity was dependent on [Ca2+]i, a large increase above resting levels was not needed, and also that some calcium was mobilized from intracellular stores. However, the caffeine-releasable pool of sarcoplasmic reticulum calcium was increased, not depleted, by exposure to 200 µ PAT. These results demonstrate that PAT disrupts [Ca2+]ihandling and support a role for a calcium-dependent event, but do not support the necessity of events in PAT-induced cell death that are mediated by a large elevation in [Ca2+]i.
Toxins; Animal-studies; Laboratory-animals; Antimony-compounds; Cardiac-function; Heavy-metals; Metal-compounds; Metallic-dusts; Particulate-dust; Dust-inhalation; Dust-exposure
H. Wey, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, 4676 Columbia Parkway, Cincinnati, Ohio, 45226
Toxicology and Applied Pharmacology