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 de termine the possible neuronal basis of these actions, the effects of both f orms of Sn were studied on identified neurones of the mollusk, Lymnaea stag nalis L. 2. SnCl2 caused a dose-dependent decrease in the acetylcholine (Ach)-induce d inward current. The effective threshold concentration, measured by a two microelectrode voltage clamp technique. was 0.1 mu M, and the maximal effec t occurred at 5 mu M SnCl2. The depression of the inward current was greate r after a 10 min preapplication (20%) than after 3 min treatment (7%). 3. The next series of experiments compared the actions of inorganic or orga nic tin compounds. In whole cell clamp experiments both (CH3)(2)SnCl2 and ( CH3)(3)SnCl, like inorganic Sn, decreased the amplitude of Ach-induced curr ent. Increasing the duration of the preapplication time resulted in an incr ease in the effect, but the action was not reversible. SnCl2 treatment caus ed a concentration-dependent alteration (initial potentiation followed by d epression) of the amplitude of I-Na(V) over the whole voltage range and sli ghtly shifted the I-V curves to the left. In contrast, trimethyl tin decrea sed the amplitude of I-Na(V) only at high concentration (100 mu M). The act ivation time course of I-Na was increased (tau = 0.43 ms in control and 0.5 5 ms in Sn), but Sn did not alter the inactivation parameters (tau = 3.43 a nd 3.41 ms). 4. These results support earlier findings that agonist- and voltage-activat ed channels are direct targets of toxic metals. We conclude that tin in bot h inorganic and organic forms acts at neuronal membranes to modulate synapt ic transmission through direct actions on agonist-activated ion channels, a nd suggest that these actions may be the basis of the altered behavior of a nimals in tin-polluted environments.