title: Altered Ca2+ mobilization during excitation-contraction in cultured cardiac myocytes exposed to antimony.
abstract: Industrial exposure and pharmaceutical use of antimony compounds have 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+]i). To determine if trivalent antimony affects [Ca2+]i during excitation-contraction, we developed an in vitro cardiac myocyte model that was exposed for 24 hr to potassium antimonyl tartrate (PAT) at 0-10 microM. Control myocytes received sodium potassium tartrate. Concentrations of up to 10 microM PAT were without effect on total DNA and protein content of cultures, indicating that PAT exposures were not overtly toxic. However, spontaneous beating rates of myocytes were significantly reduced by 5 and 10 microM PAT. Myocytes were paced by electric field stimulation at 0.5 Hz, and the effect of PAT on [Ca2+]i transients during excitation-contraction was monitored with fura-2. PAT (2-8 microM) significantly reduced systolic [Ca2+]i in a concentration-dependent fashion, but was without effect on diastolic [Ca2+]i or on the first derivative of the transient rise (d[Ca2+]i/dt). Myocytes from control cells responded to epinephrine (10(-8)-10(-5) m) in concentration-dependent fashion with elevated systolic [Ca2+]i and an increase in the rate of decay of transients. In PAT-exposed myocytes, the systolic response was blunted while the decay rate was enhanced. PAT-exposed cells also exhibited a reduced basal [Ca2+]i when depolarized by 90 mm KCl and a reduced caffeine-releasable Ca2+ pool of the sarcoplasmic reticulum. Both control and PAT-treated cells responded to ryanodine in a comparable fashion. Results indicate that a nonlethal exposure to PAT reduces Ca2+ availability during excitation-contraction. Decreased influx of Ca2+ across the sarcolemma and enhanced removal of Ca2+ appear to be responsible.
authors.affiliation: Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, 4676 Columbia Parkway, Cincinnati, Ohio 45226, USA.
authors.forename: M
authors.initials: M
authors.lastname: Toraason
authors.forename: H E
authors.initials: HE
authors.lastname: Wey
authors.forename: D E
authors.initials: DE
authors.lastname: Richards
authors.forename: P I
authors.initials: PI
authors.lastname: Mathias
authors.forename: E
authors.initials: E
authors.lastname: Krieg
mesh_terms: D000818:Animals; D000965:Antimony / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology; D020746:Calcium Channels, L-Type; D002478:Cells, Cultured; D004247:DNA / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D011189:Potassium Chloride; D004247:DNA; D000965:Antimony; D002118:Calcium; D004837:Epinephrine