Ion channels and control of motility in the liver fluke fasciola hepatica

Throughout the course of this Thesis, a range of different, yet parallel, experimental techniques were employed to investigate ion channels and control of motility in the liver fluke. In the first experimental study, voltage-gated potassium channels and control of motility were investigated using isometric tension recording studies. All of the classical potassium channel blockers employed had some form of excitatory effect on spontaneous contractions of the liver fluke. Of the more selective blockers tested, only the Kv I subfamily blocker, correolide, and the Kv 1.4 subtype blockers, zero potassium solution and riluzole, had any affect on spontaneous contractions. The results suggest a functional role for voltage-gated potassium channels in the contractility of fluke body wall, and imply that the Kv1.4 subtype may be involved. In the second experimental study, calmodulin and control of motility in the liver fluke was investigated. Immunohistochemical studies showed calmodulin immunostaining in all three ofthe welldistinguished muscle systems ofthe fluke, in addition to the vitelline cells and neural tissue. However, none of the calmodulin or myosin light chain kinase inhibitors had any effect on the spontaneous contractions of the fluke body muscle strips in isometric tension recordings. The results suggest that calmodulin plays a role in muscle systems as well as vitelline cells and neural tissue however its involvement in contractility is still not clear. The final experimental study investigated voltage-gated calcium channels and calcium store release channels and control of motility in the fluke. Findings from isometric tension recordings revealed that all of the mammalian L-type calcium channel blockers effected spontaneous contractions of the fluke body muscle, suggesting that L-type calcium channels play functional roles in fluke contractility and have similarity to mammalian L-type calcium channels. Such findings were supported by sequencing of part of a fluke (1.1 subunit, which was found to share 75% identity to the corresponding region of a channel subunit in Schistosoma mansoni, and this protein most closely resembles an L-type calcium channel in vertebrates.