| Metal Particulate Matter Components Affect Gene Expression and Beat Frequency of Neonatal Rat Ventricular Myocytes Donald W. Graff,1 Wayne E. Cascio,2,3 Joseph A.
Brackhan,2 and Robert B. Devlin1 1National Health and Environmental Effects Research Laboratory,
U.S. Environmental Protection Agency, Research Triangle Park,
North Carolina, USA; 2Division of Cardiology, Department of Medicine,
and 3Asthma and Lung Biology, The Center for Environmental Medicine,
University of North Carolina, Chapel Hill, North Carolina, USA Abstract
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 µM) for 6 hr produced significant increases in IL-6, IL-1 , 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 1 subunit of the L-type calcium channel, and Cx43, as well as IL-6 and IL-1. 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. Key words: beat frequency, cardiac myocytes, cytokines, gap junctions, ion channels, metals, particulate matter. Environ Health Perspect 112:792-798 (2004) . doi:10.1289/txg.6865 available via http://dx.doi.org/ [Online 12 April 2004]
Address correspondence to D. Graff, National Health and Environmental Effects Research Laboratory, U.S. EPA, MD 58D, Research Triangle Park, NC 27711 USA. Telephone: (919) 843-5155. Fax: (919) 966-6271. E-mail: graff.don@epa.gov We acknowledge L. Dailey and R. Silbajoris for their work on the RT-PCR experiments, and K. Dreher and J. Samet for their careful review of this manuscript. The information described in this article has been reviewed by the National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, and has been approved for publication. Approval does not signify that the contents necessarily reflect the views and policy of the agency, nor does mention of trade names or commercial products constitute endorsement or recommendation of use. The authors declare they have no competing financial interests. Received 17 November 2003 ; accepted 7 April 2004.
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