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Invert Neurosci. 2007 Mar;7(1):3-16. Epub 2007 Feb 9.

Pyrethroid action on calcium channels: neurotoxicological implications.

Author information

1
Department of Veterinary and Animal Science, University of Massachusetts, Morrill 1 N311, 639 N. Pleasant St., Amherst, MA 01003, USA. jclark@vasci.umass.edu

Abstract

Actions of cismethrin versus deltamethrin were compared using two functional attributes of rat brain synaptosomes. Both pyrethroids increased calcium influx but only deltamethrin increased Ca(2+)-dependent neurotransmitter release following K(+)-stimulated depolarization. The action of deltamethrin was stereospecific, concentration-dependent, and blocked by omega-conotoxin GVIA. These findings delineate a separate action for deltamethrin and implicate N-type rat brain Ca(v)2.2 voltage-sensitive calcium channels (VSCC) as target sites that are consistent with the in vivo release of neurotransmitter caused by deltamethrin. Deltamethrin (10(-7) M) reduced the peak current (approx. -47%) of heterologously expressed wild type Ca(v)2.2 in a stereospecific manner. Mutation of threonine 422 to glutamic acid (T422E) in the alpha(1)-subunit results in a channel that functions as if it were permanently phosphorylated. Deltamethrin now increased peak current (approx. +49%) of T422E Ca(v)2.2 in a stereospecific manner. Collectively, these results substantiate that Ca(v)2.2 is directly modified by deltamethrin but the resulting perturbation is dependent upon the phosphorylation state of Ca(v)2.2. Our findings may provide a partial explanation for the different toxic syndromes produced by these structurally-distinct pyrethroids.

PMID:
17294162
DOI:
10.1007/s10158-006-0038-7
[Indexed for MEDLINE]

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