Citation:

SHAFER, T. J. AND P. J. BUSHNELL. TRICHLOROETHYLENE IHIBITS VOLTAGE-SENSITIVE CALCIUM CURRENTS IN DIFFERENTIATED PC 12 CELLS. Presented at Society of Toxicology, San Diego, CA, March 05 - 09, 2006.

Description:

ABSTRACT BODY: It has been demonstrated recently that volatile organic compounds (VOCs)such as toluene, perchloroethylene and trichloroethylene inhibit function of voltage-sensitive calcium channels (VSSC). Such actions are hypothesized to contribute to the acute neurotoxicity of VOCs, as the potency of effects in vitro is consistent with the potency of effects in vivo. To test this hypothesis further, a structure-activity relationship (SAR) for VOC effects on VSSC is being constructed. Toward this end, effects of trichloroethane (TCA) on whole-cell calcium currents (ICa) in nerve growth factor-differentiated PC12 cells were determined using patch clamp techniques. Like other VOCs, TCA inhibited ICa in a concentration-dependent manner. Inhibition was <10% at a nominal concentration of 1 mM TCA and exceeded 90% at a nominal concentration of 12 mM (n= 3-5 cells/concentration). The estimated IC50 for TCA was approximately 7 mM. Other parameters of TCA effects on ICa were identical to those of other VOCs: end current was slightly more sensitive to inhibition by TCA than was peak current, and inactivation of ICa during the depolarizing test pulse changed from a single exponential function in the absence of TCA to a double exponental function in its presence. These data demonstrate that TCA, like toluene, xylene, trichloroethylene and perchloroethylene, inhibits VSSC function, and provides additional data from which to construct a SAR relationship for solvent effects on VSSC. (This is an abstract of a proposed presentation and does not necessarily reflect EPA policy. Mention of trade names or commerical products does not constitute endorsement or recommendation of use.)

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