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.