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Antimony attenuates mobilization of CA during excitation and contraction in cultured cardiac myocytes.
Wey HE; Richards DE; Mathias PI; Kreig E; Toraason M
Toxicologist 1997 Mar; 36(1)(Pt 2):46
Industrial and pharmaceutical use of antimony compounds has been linked to altered cardiovascular function and pathology. Antimony compounds induce hypotension, bradycardia, and cardiac arrhythmias all of which can arise from aberrations in myocyte regulation of intracellular free calcium concentration ([Ca2+]). In order to investigate the effects of trivalent antimony on [Ca2+], we developed an in vitro cardiac myocyte model that was exposed for 24 hr to potassium antimonyl tartrate (PAT) at 0-10 uM. Control myocytes were exposed to sodium potassium tartrate. Cardiac myocytes were obtained from neonatal rats and maintained in M 199 supplemented with 10% calf serum for 2 days prior to exposure to PAT. Culture concentrations of up to 10 uM PAT were without effect on total DNA and protein content of cultures indicating that PAT exposures were not overtly toxic. Spontaneous beating rate of myocytes was significantly reduced by 5 or 10 J.LM PAT. [Ca2+]i transients were monitored with fura-2 during excitation in myocytes paced by electric field stimulation at 0.5 Hz. Myocytes exposed to 8 uM PAT were often not paceable, therefore, the maximum exposure concentration evaluated was 6 uM. PAT significantly reduced systolic [Ca2+] in a concentration-dependent fashion, but was without effect on diastolic [Ca2+], the first derivative of the transient rise (d[Ca2+ ]/dt), or the exponential decay of the transient. Myocytes from control cells responded to epinephrine (10^-8 -10^5M) in concentration-dependent fashion with elevated systolic [Ca2+] and an increase in the rate of decay of transients. In PAT-exposed myocytes, the systolic response was blunted while the decay-rate response was maintained. PATexposed cells also exhibited a reduced basal [Ca2+] when depolarized by 90 mM KC 1, and a reduced caffeine-releasable Ca2+ pool of the sarcoplasmic reticulum (SR). Both control and PAT treated cells responded to ryanodine in a comparable fashion. Results indicate that a nonlethal exposure to PAT impairs Ca2+ mobilization during excitation and contraction. Decreased flux of Ca2+ across the sarcolemlna and a reduced SR-Ca2+ pool appear to be primarily responsible.
Toxins; Toxic-materials; Toxic-effects; Myocardial-disorders; Myocardium; Cardiac-function; Heart; Antimony-compounds
Issue of Publication
The Toxicologist. Society of Toxicology 36th Annual Meeting, March 9-13, 1997, Cincinnati, Ohio
Page last reviewed: April 9, 2021
Content source: National Institute for Occupational Safety and Health Education and Information Division