Role of calcium and calmodulin in Giardia lamblia-induced diarrhoea in mice.

The unidirectional fluxes of Na+, Cl- and Ca2+ across the small intestinal epithelium of normal and Giardia lamblia-infected mice were studied in vitro in short-circuited tissue. Net secretion of Na+ and Cl- was observed in infected animals, whereas in non-infected (control) animals there was net absorption of Na+ ions and marginal secretion of Cl- ions. In infected animals, net absorption of Ca2+ was observed as compared to little secretion observed in control animals. Although the presence of Ca(2+)-ionophore in the medium resulted in a net secretion of Na+ and Cl- in controls, it could not cause any change in the fluxes of these ions in infected animals. Verapamil, a calcium channel blocker, reversed the effects of infection and Ca(2+)-ionophore. Further W7 (n-(6-aminohexyl)-5 chloro-1-naphthalene sulphonamide), a calmodulin antagonist, also reversed the effects of infection. The addition of the neurotoxin, tetrodotoxin caused net absorption of Na+, Cl- and net secretion of Ca2+ in the control group, but it could not produce any effect on the fluxes of these ions in the infected group. These findings demonstrate that, in G. lamblia infection, the secretion of Na+ and Cl- is associated with an increase in absorption of Ca2+ and an increase in calmodulin activity in intestinal microvillar core. These findings further suggest that the enteric nervous system plays a marginal role in Giardia infection.