Neurobiological processes play an important role in the survival and reproductive fitness of Schistosoma mansoni, a very small but medically important helminth. Previous attempts, to define the exact physiological and/or biochemical mechanisms, by which this parasite regulates its muscle cell activity, have been limited by the size of the parasite and the absence of electrophysiological methods to study small muscle cells. With the advent of a method for isolating single muscle fibers from the adult schistosomes it is now possible, through the use of an electrophysiological method called patch voltage-clamping, to characterize the properties of the various ion channels located on the surface of these muscle fibers.
Our specific aim i s to utilize this method to characterize the properties of the various ion channels in the membrane of schistosome muscle fibers by analyzing total ionic currents across this membrane or unitary currents through single ion channels. This will be accomplished through manipulation of the inorganic and/or organic environment around the intact or isolated muscle cell membrane. Through these manipulations we will characterize those ion channels which play a major role in regulating muscle cell function, determine how neurotransmitter and/or second messengers affect these channels and analyze the action of a major antischistosomal compound. Collectively, and for the first time, data from these experiments will provide unequivocal information as to how ion channels regulate muscle cell function, the role that neurotransmitters play in regulating their activity and whether a major antischistosomal agent interferes with ion channels located on these cells. Results from these studies should provide much more detailed information that will be relevant to our overall long term goal of identifying unique schistosome mechanisms for regulating neurobiological processes that will allow for the development of antischistosomal agents that will be selective in their action.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI030465-01A1
Application #
3145443
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Project Start
1991-08-01
Project End
1994-07-31
Budget Start
1991-08-01
Budget End
1992-07-31
Support Year
1
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Michigan State University
Department
Type
Schools of Arts and Sciences
DUNS #
193247145
City
East Lansing
State
MI
Country
United States
Zip Code
48824
Cobbett, Peter; Day, Timothy A (2003) Functional voltage-gated Ca2+ channels in muscle fibers of the platyhelminth Dugesia tigrina. Comp Biochem Physiol A Mol Integr Physiol 134:593-605
Day, T A; Haithcock, J; Kimber, M et al. (2000) Functional ryanodine receptor channels in flatworm muscle fibres. Parasitology 120 ( Pt 4):417-22
Miller, C L; Day, T A; Bennett, J L et al. (1996) Schistosoma mansoni: L-glutamate-induced contractions in isolated muscle fibers;evidence for a glutamate transporter. Exp Parasitol 84:410-9
Day, T A; Chen, G Z; Miller, C et al. (1996) Cholinergic inhibition of muscle fibres isolated from Schistosoma mansoni (Trematoda:Digenea). Parasitology 113 ( Pt 1):55-61
Day, T A; Bennett, J L; Pax, R A (1994) Serotonin and its requirement for maintenance of contractility in muscle fibres isolated from Schistosoma mansoni. Parasitology 108 ( Pt 4):425-32
Day, T A; Orr, N; Bennett, J L et al. (1993) Voltage-gated currents in muscle cells of Schistosoma mansoni. Parasitology 106 ( Pt 5):471-7