Binary mixtures of pyrethroids crosstalk between voltage-sensitive calcium and chloride channels in isolated presynaptic nerve terminals from rat brain

AGRO 34

Hilliary E. Hodgdon, hhodgdon@vasci.umass.edu1, Richard K. Frisbie, rfrisbie@mcb.umass.edu2, and John M. Clark, jclark@vasci.umass.edu1. (1) Department of Veterinary and Animal Science, University of Massachusetts, 639 North Pleasant st, Morrill I, Rm. N429, Amherst, MA 01003, (2) Molecular and Cellular Biology Program, University of Massachusetts, 639 North Pleasant Street, Morrill I, N429, Amherst, MA 01003
Target sites other than voltage-sensitive sodium channels (VSSCs) are implicated in the neurotoxic response of pyrethroids. Both voltage-sensitive calcium (VSCCs) and chloride channels (VSClCs) are modified by pyrethroids in a stereospecific manner at toxicologically relevant concentrations. Our most recent research is focused on the cumulative risk of pyrethroids since environmental exposure to pyrethroids usually involves exposure to multiple compounds. Isolated presynaptic nerve terminals (synaptosomes) are an ideal in vitro model system to study the effects of pyrethroids since virtually all functional aspects of presynaptic nerve terminals are retained. Our results revealed that certain binary mixtures, which had deltamethrin as one of the pyrethroids, produced a more-than-additive effect on neurotransmitter release that was not calcium dependent. All of these mixtures had pyrethroids that act as VSClC antagonists, suggesting crosstalk between VSClCs and VSCCs. We will validate this assumption by using a chloride channel antagonist, rChlorotoxin, and a chloride channel agonist, pentobarbital.
 

Agrochemical Education Awards For Graduate Student Travel
8:00 AM-11:00 AM, Monday, August 20, 2007 BCEC -- Exhibit Hall - B2, Poster

Division of Agrochemicals

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007