Effect of inorganic and organic tin compounds on ACh- and voltage-activated Na currents

1. Inorganic tin and organotin compounds, occurring in aquatic ecosystems, are toxic and can cause behavioral abnormalities in living organisms. To determine the possible neuronal basis of these actions, the effects of both forms of Sn were studied on identified neurones of the mollusk, Lymnaea stagnalis L. 2. SnCl2 caused a dose-dependent decrease in the acetylcholine (Ach)-induced inward current. The effective threshold concentration, measured by a two microelectrode voltage clamp technique, was 0.1 microM, and the maximal effect occurred at 5 microM SnCl2. The depression of the inward current was greater after a 10 min preapplication (20%) than after 3 min treatment (7%). 3. The next series of experiments compared the actions of inorganic or organic tin compounds. In whole cell clamp experiments both (CH3)2SnCl2 and (CH3)3SnCl, like inorganic Sn, decreased the amplitude of Ach-induced current. Increasing the duration of the preapplication time resulted in an increase in the effect, but the action was not reversible. SnCl2 treatment caused a concentration-dependent alteration (initial potentiation followed by depression) of the amplitude of I(Na(V)) over the whole voltage range and slightly shifted the I-V curves to the left. In contrast, trimethyl tin decreased the amplitude of I(Na(V)) only at high concentration (100 microM). The activation time course of I(Na) was increased (tau = 0.43 ms in control and 0.55 ms in Sn), but Sn did not alter the inactivation parameters (tau = 3.43 and 3.41 ms). 4. These results support earlier findings that agonist- and voltage-activated channels are direct targets of toxic metals. We conclude that tin in both inorganic and organic forms acts at neuronal membranes to modulate synaptic transmission through direct actions on agonist-activated ion channels, and suggest that these actions may be the basis of the altered behavior of animals in tin-polluted environments.