Campus Units
Biomedical Sciences
Document Type
Article
Publication Date
8-10-2010
Journal or Book Title
PLoS Neglected Tropical Diseases
Volume
4
Issue
8
First Page
e790
DOI
10.1371/journal.pntd.0000790
Abstract
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.
Rights
This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Copyright Owner
Novozhilova et al.
Copyright Date
2010
Language
en
File Format
application/pdf
Recommended Citation
Novozhilova, Ekaterina; Kimber, Michael J.; Qian, Hai; McVeigh, Paul; Robertson, Alan P.; Zamanian, Mostafa; Maule, Aaron G.; and Day, Timothy A., "FMRFamide-Like Peptides (FLPs) Enhance Voltage-Gated Calcium Currents to Elicit Muscle Contraction in the Human Parasite Schistosoma mansoni" (2010). Biomedical Sciences Publications. 18.
https://lib.dr.iastate.edu/bms_pubs/18
Comments
This article is from PLoS Negl Trop Dis 4(8): e790. doi:10.1371/journal.pntd.0000790. Posted with premission.