Antimony alters kinetics of calcium transients of neonatal rat cardiac myocytes.
Wey-H; Richards-D; Mathias-P; Tirmenstein-M; ToraasON-M
Toxicologist 1996 Mar; 30(1)(Part 2):270
Cardiotoxicity has long been associated with exposure to antimony compounds. Effects in humans exposed to trivalent forms of antimony include hypotension, bradycardia, ventricular tachycardia, electrocardiographic changes and sudden death. The present study describes the effects of overnight exposure to a nonlethal concentration of potassium antimonyl tartrate (PAT) on calcium transients in neonatal rat cardiac myocytes. Isolated cardiac myocytes were cultured on glass coverslips and after 2 days were exposed overnight to 2 uM PAT in medium with 10% serum. Both control and PAT-treated cells were beating and indistinguishable in microscopic morphology. Myocytes loaded with the fluorescent probe fura-2 were paced at 0.5 Hz using field stimulation and [Ca2+]1 monitored on an inverted phase contrast microscope. The calcium transient was expressed as changes in the ratio of fluorescence at 340nm to 380 nm. For each cell, the average [Ca2+1 transient was obtained from 15 individual transients. This was done for 3-5 cells per treatment in replicate experiments. Transients were characterized by 1) the basal "diastolic" ratio (D); 2) the peak amplitude of the ratio (A); and 3) the decrease in the ratio that follows A, as expressed by the rate constant of decay (k) that was determined by fitting the data to an exponential. Cells treated with 2 uM PAT exhibited a small increase in diastolic ratio (105% of control), a reduction in peak amplitude (73% of control), and a decrease in k (70% of control). Treatment of PAT-exposed and control cells with isoproterenol (10-7 M) altered the [Ca2+]1 transient of both groups consistent with a adrenergic effect. The effect of PAT on diastolic ratio was maintained (110% of control), whereas A and k were comparable between control and PAT-treated cells. The demonstrated effects of antimony on [Ca2+]1 transients in contracting myocytes could be a factor in the cardiac arrhythmias observed in humans exposed to antimony.
Laboratory-animals; Animals; Animal-studies; Calcium-compounds; Antimony-compounds; Exposure-levels; Exposure-assessment; Morphology
The Toxicologist. Society of Toxicology 35th Annual Meeting, March 10-14,1996, Anaheim, California