Metal particulate matter components affect gene expression and beat frequency of neonatal rat ventricular myocytes.
Soluble particulate matter (PM) components (e.g., metals) have the potential to be absorbed into the bloodstream and transported to the heart where they might induce the expression of inflammatory cytokines and remodel electrical properties. We exposed cultured rat ventricular myocytes to similar concentrations of two metals [zinc (Zn) and vanadium (V)] found commonly in PM and measured changes in spontaneous beat rate. We found statistically significant reductions in spontaneous beat rate after both short-term (4-hr) and long-term (24-hr) exposures, with a more substantial effect seen with Zn. We also measured the expression of genes associated with inflammation and a number of sarcolemmal proteins associated with electrical impulse conduction. Exposure to Zn or V (6.25-50 microM) for 6 hr produced significant increases in IL-6, IL-1 alpha, heat shock protein 70, and connexin 43 (Cx43). After 24 hr exposure, Zn induced significant changes in the gene expression of Kv4.2 and KvLQt (potassium channel proteins), the alpha 1 subunit of the L-type calcium channel, and Cx43, as well as IL-6 and IL-1 alpha. In contrast, V produced a greater effect on Cx43 and affected only one ion channel (KvLQT1). These results show that exposure of rat cardiac myocytes to noncytotoxic concentrations of Zn and V alter spontaneous beat rate as well as the expression of ion channels and sarcolemmal proteins relevant to electrical remodeling and slowing of spontaneous beat rate, with Zn producing a more profound effect. As such, these data suggest that the cardiac effects of PM are largely determined by the relative metal composition of particles.
Graff
Donald W
DW
National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA. graff.don@epa.gov
Cascio
Wayne E
WE
Brackhan
Joseph A
JA
Devlin
Robert B
RB
D000818:Animals; D000831:Animals, Newborn; D016207:Cytokines / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D006339:Heart Rate / Q000187:drug effects*; D006352:Heart Ventricles / Q000166:cytology / Q000473:pathology; D007249:Inflammation; D007473:Ion Channels; D032342:Muscle Cells / Q000473:pathology*; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014639:Vanadium / Q000633:toxicity*; D015032:Zinc / Q000633:toxicity*
D016207:Cytokines; D007473:Ion Channels; D014639:Vanadium; D015032:Zinc