FMRFamide-Like Peptides (FLPs) Enhance Voltage-Gated Calcium Currents to Elicit Muscle Contraction in the Human Parasite Schistosoma mansoni Novozhilova, Ekaterina Kimber, Michael Qian, Hai McVeigh, Paul Robertson, Alan Zamanian, Mostafa Maule, Aaron Day, Timothy
dc.contributor.department Biomedical Sciences 2018-02-17T15:31:54.000 2020-06-30T00:53:06Z 2020-06-30T00:53:06Z Fri Jan 01 00:00:00 UTC 2010 2010-08-10
dc.description.abstract <p>Schistosomes are amongst the most important and neglected pathogens in the world, and schistosomiasis control relies almost exclusively on a single drug. The neuromuscular system of schistosomes is fertile ground for therapeutic intervention, yet the details of physiological events involved in neuromuscular function remain largely unknown. Short amidated neuropeptides, FMRFamide-like peptides (FLPs), are distributed abundantly throughout the nervous system of every flatworm examined and they produce potent myoexcitation. Our goal here was to determine the mechanism by which FLPs elicit contractions of schistosome muscle fibers. Contraction studies showed that the FLP Tyr-Ile-Arg-Phe-amide (YIRFamide) contracts the muscle fibers through a mechanism that requires Ca2+ influx through sarcolemmal voltage operated Ca2+ channels (VOCCs), as the contractions are inhibited by classical VOCC blockers nicardipine, verapamil and methoxyverapamil. Whole-cell patch-clamp experiments revealed that inward currents through VOCCs are significantly and reversibly enhanced by the application of 1 µM YIRFamide; the sustained inward currents were increased to 190% of controls and the peak currents were increased to 180%. In order to examine the biochemical link between the FLP receptor and the VOCCs, PKC inhibitors calphostin C, RO 31–8220 and chelerythrine were tested and all produced concentration dependent block of the contractions elicited by 1 µM YIRFamide. Taken together, the data show that FLPs elicit contractions by enhancing Ca2+ influx through VOCC currents using a PKC-dependent pathway.</p>
dc.description.comments <p>This article is from PLoS Negl Trop Dis 4(8): e790. doi:<a href="" target="_blank">10.1371/journal.pntd.0000790</a>. Posted with premission.</p>
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dc.identifier archive/
dc.identifier.articleid 1017
dc.identifier.contextkey 8403819
dc.identifier.s3bucket isulib-bepress-aws-west
dc.identifier.submissionpath bms_pubs/18
dc.language.iso en
dc.source.bitstream archive/|||Fri Jan 14 21:33:59 UTC 2022
dc.source.uri 10.1371/journal.pntd.0000790
dc.subject.disciplines Neuroscience and Neurobiology
dc.subject.disciplines Parasitic Diseases
dc.subject.keywords Muscle contraction
dc.subject.keywords Muscle fibers
dc.subject.keywords Schistosoma
dc.subject.keywords Flatworms
dc.subject.keywords Schistosoma mansoni
dc.subject.keywords Muscle biochemistry
dc.subject.keywords Neuropeptides
dc.subject.keywords Schistosomiasis
dc.title FMRFamide-Like Peptides (FLPs) Enhance Voltage-Gated Calcium Currents to Elicit Muscle Contraction in the Human Parasite Schistosoma mansoni
dc.type article
dc.type.genre article
dspace.entity.type Publication
relation.isAuthorOfPublication 18a862f2-47df-421c-9594-61cfea624d28
relation.isOrgUnitOfPublication 184db3f2-d93f-4571-8ad7-07c8a9e6a5c9
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