Lithium attenuates the active transport of calcium in the larva of Aëdes aegypti

We now present evidence that lithium ions (Li⁺) act in a similar manner to that of ruthenium-red in attenuating the accumulation of Ca²⁺ from dilute solutions. The net Ca²⁺ uptake and the Ca²⁺ fluxes were estimated with ⁴⁵Ca in early fourth instar larvae. The net Ca²⁺ uptake (nmol h^-1 larva^-1) was determined at Ca²⁺ concentrations ranging between 0·01 and 50 mm in the presence and absence of 2mm-LiCl or 2mm-NaCl. Calcium fluxes were determined at a concentration of 0·1 mm-CaCl₂ from the curve representing the accumulation of ⁴⁵Ca in the larva with time (Barkai & Williams, 1983).

The effects of Li⁺ on the saturable transport of calcium were studied in separate experiments. The saturable transport was analysed, according to the method of Lineweaver & Burk (1934), in the presence and absence of Li⁺ (2mm). This analysis revealed that the maximum transport velocity (Vmax) decreased markedly in the presence of LiCl (Fig. 2), a phenomenon which was not observed with NaCl. The apparent affinity constant (Km) was not appreciably different. These results indicate that a marked decrease had occurred in the number of ‘calcium carriers’ when the larvae were exposed to LiCl and show that Li⁺ may influence carrier sites which are linked to the Ca²⁺ pump. The finding that Li⁺ acts to increase K_out and decrease K_in in a manner similar to that of ruthenium-red (Table 1) suggests that Li⁺ influences two independent processes; one is the absorption of Ca²⁺ from dilute solutions into the larva and the other is the prevention of Ca²⁺ loss to the medium. The entry of Ca²⁺ is most likely to occur through the gut, whereas Ca²⁺ loss occurs in the urine. Lithium may therefore interfere with the action of calcium pumps which are located in both the gut and the rectum. The calcium pumps in the gut act to enhance the entry of Ca²⁺ from the swallowed medium, and therefore inhibition of their activity is expected to result in a lower K_in In contrast, the calcium pumps in the rectum act to reabsorb Ca²⁺ that has been excreted in the urine by the Malpighian tubules, and therefore inhibition of their activity might be expected to result in a higher K_out.

Effects of Li⁺ on Ca²⁺ transport are of some importance in biological psychiatry in view of the therapeutic role of Li⁺ in the treatment of affective disorders (Shopsin & Gershon, 1978). Although Li⁺ is widely used in psychiatry, its mode of action has not yet been elucidated. It has been suggested that Li⁺ acts at the presynaptic membrane, preventing release of biogenic amines and facilitating their uptake (Bunney, Gershon, Murphy & Goodwin, 1972), probably by inhibiting the action of Ca²⁺ on the presynaptic membrane (Katz & Kopin, 1968), but direct evidence for the antagonism between Li⁺ and Ca²⁺ is still obscure. The uptake of Li⁺ into rat cerebral cortex slices has been shown to be inversely related to the concentrations of Ca²⁺ in the medium (Wraae, Hillman & Round, 1976). Recent studies with red blood cells indicated that Li⁺ and Ca²⁺ may share the same transport system (Meltzer, 1979), thus implying that the therapeutic effects of Li⁺ in certain affective disorders may be associated with changes in calcium transport.

The present findings that Li⁺ but not Na⁺ inhibits the active transport of Ca²⁺ in the mosquito larva is consistent with the observation that Li⁺ efflux is linked to the operation of Ca²⁺ pumps in the red blood cell (Meltzer, 1979) and suggests that larvae of Aëdes aegypti provide a useful and convenient model to study the effects of Li⁺, or other agents, on the saturable system for the active transport of calcium.