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The Pyrethroid Deltamethrin, Which Causes Choreoathetosis with Salivation (CS-Syndrome), Enhances Calcium Ion Influx via Phosphorylated CaV2.2 expresssed in Xenopus laevis oocytes

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dc.contributor.advisorJohn M. Clark
dc.contributor.advisorSteven B. Symington
dc.contributor.authorAlves, Anna-maria
dc.contributor.departmentUniversity of Massachusetts Amherst
dc.contributor.departmentMolecular & Cellular Biology
dc.date2023-09-23T04:41:17.000
dc.date.accessioned2024-04-26T21:16:16Z
dc.date.available2011-10-11T00:00:00Z
dc.date.issued2012-01-01
dc.date.submittedFebruary
dc.description.abstractPyrethroids are insecticides used since the 1970s. They are favored for their low mammalian toxicity, improved environmental stability and insecticidal potency. Voltage-gated sodium channels (VGSCs) are a known target but in vitro evidence indicates that voltage-gated calcium channels (VGCCs) are also targets. Site-directed mutagenesis of CaV2.2 (N-type), altering threonine 422 to glutamate (T422E), produces a mutant channel that acts as if permanently phosphorylated. Deltamethrin increases peak current of T422E CaV2.2 compared to its antagonistic action on wild type CaV2.2 when expressed in Xenopus oocytes. Phosphorylation of wild type CaV2.2 is evoked by the phorbol ester PMA by activating endogenous protein kinase C (PKC) in oocytes. Under steady-state conditions, deltamethrin increases transient peak current and slows deactivation kinetics of the PKC phosphorylated channel thereby increasing Ca2+ influx and neurotransmitter release. Conversely, deltamethrin treatment resulted in no effect on the deactivation kinetics of the unphosphorylated or T422E channels. Under voltage-dependent conditions, deltamethrin enhances peak current, and causes a hyperpolarizing shift in activation midpoint potential of the PKC phosphorylated channel which is consistent with enhanced Ca2+ influx. The hyperpolarizing shift of activation midpoint potential was not observed when deltamethrin was applied to the T422E mutant channels indicating that the other phosphorylation sites on CaV2.2 may be playing a role in the differential effects observed in the action of deltamethrin on the unphosphorylated channel, the T422E mutant and the PMA-activated PKC phosphorylation channel.
dc.description.degreeMaster of Science (M.S.)
dc.identifier.doihttps://doi.org/10.7275/2288902
dc.identifier.urihttps://hdl.handle.net/20.500.14394/47697
dc.relation.urlhttps://scholarworks.umass.edu/cgi/viewcontent.cgi?article=1847&context=theses&unstamped=1
dc.source.statuspublished
dc.subjectdeltamethrin
dc.subjectCaV2.2
dc.subjectPMA
dc.titleThe Pyrethroid Deltamethrin, Which Causes Choreoathetosis with Salivation (CS-Syndrome), Enhances Calcium Ion Influx via Phosphorylated CaV2.2 expresssed in Xenopus laevis oocytes
dc.typeopen
dc.typearticle
dc.typethesis
digcom.contributor.authorisAuthorOfPublication|email:annamariaalves@gmail.com|institution:University of Massachusetts Amherst|Alves, Anna-maria
digcom.date.embargo2011-10-11T00:00:00-07:00
digcom.identifiertheses/777
digcom.identifier.contextkey2288902
digcom.identifier.submissionpaththeses/777
dspace.entity.typePublication
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