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AN IP3 RECEPTOR-SENSITIVE CALCIUM STORE MEDIATES DISTURBANCES IN INTRACELLULAR CALCIUM UPON EXPOSURE TO AROCLOR 1254 AND ORTHO-SUBSTITUTED PCBS.
Citation:
Inglefield, J R., W R. Mundy, AND T J. Shafer. AN IP3 RECEPTOR-SENSITIVE CALCIUM STORE MEDIATES DISTURBANCES IN INTRACELLULAR CALCIUM UPON EXPOSURE TO AROCLOR 1254 AND ORTHO-SUBSTITUTED PCBS. Presented at Am. Society of Pharmacology and Experimental Therapeutics, Boston, MA, June 4-8, 2000.
Description:
An IP3 Receptor-Sensitive Ca2+ Store Mediates Disturbances In Intracellular Ca2+ Upon Exposure To Aroclor 1254 And Ortho-Substituted PCBs JR Inglefield, WR Mundy, and TJ Shafer. Neurotoxicol. Div., NHEERL, US EPA, RTP, NC. Sponsor: L Birnbaum
Polychlorinated biphenyls (PCBs) are bio-accumulative toxicants that elicit a broad spectrum of biochemical responses in many cell types. Previously, we found that Aroclor 1254 (A1254, UltraScientific Inc.; 1- 20 mM; 0.3-6 ppm), a PCB mixture, elicited recurring oscillations of intracellular calcium (Ca) (latency 8-20 min, duration 15-60 sec, max. frequency 2 min-1) in cultured neonatal cortical cells (cultured < 8 d.) that were mediated by L-type Ca channel activation (Neurosci. Abstr. 25, 500.17). Cellular responses to A1254 consisted of an immediate, transient increase of Ca, reaching 1 mM with 20 mM A1254 from baseline 0.1 mM (latency < 0.5 min), that was typically followed by Ca oscillations. Here, using single cell fura-2 imaging, the mechanism(s) for the A1254-stimulated Ca transient (1- 25 mM) was examined as was the ability of individual dioxin-like (non-ortho-substituted; IUPAC 15, 77, 126) and non-dioxin-like (ortho- substituted; IUPAC 4, 138) PCB congeners (5- 10 mM) to elicit a Ca transient. Ca transients were elicited by ortho- but not non-ortho-substituted PCBs. Initial Ca disturbances by PCBs did not depend on extracellular Ca or L-type Ca channels. Block of the Ca transient with 10 mM thapsigargin confirmed intracellular Ca pools as the Ca source for the transient. A1254 Ca transients were also blocked by Xestospongin C (1 mM) pre-treatment, an IP3-receptor antagonist, but not affected by RyR antagonism (with 100 mM ryanodine). The results indicate ortho-substituted PCBs in A1254 cause an initial Ca transient that is dependent on IP3 receptor-gated Ca stores. This abstract does not necessarily reflect US EPA policy.