Selective transport of Li⁺ across lipid bilayer membranes mediated by an ionophore of novel design (ETH1644)

The neutral noncyclic, lithium-selective ionophore ETH1644, which is structurally different from previously available ionophores of this type, is a selective carrier of Li^- in lipid bilayer membranes of various lipid composition. The ionophore forms a 2:1 carrier/cation complex, and the rate-limiting step in the overall transport process is the diffusion of the carrier/ion complex across the membrane. The selectivity sequence for lithium vs. other ions normally found in biological systems is: Li⁺ (1)>Na⁺ (0.017)≥K⁺ (0.017) >Cl^- (0.001), Ca²⁺ and Mg²⁺ are impermeant. At neutral pH protons do not interfere with the Li⁺-carrying ability of this ionophore. On the basis of structural differences and supported by conductance data, it is argued that the improved selectivity of Li⁺ over the other alkali cations is due more to a decrease in the affinities of the ionophore for the latter cations that to an increase of its affinity to Li⁺. This ionophore can also act as a carrier of biogenic amines (catecholes, indoles and derivatives), with the structure of the permeant species and mechanism of permeation similar to that observed with the alkali cations. The selectivity sequence is: tryptamine (18.1)>phenylethylamine (11.6)> tyramine (2.4)>Li⁺(1)>serotonin (0.34)>epinephrine (0.09) >dopamine (0.05)>norepinephrine (0.02), showing the ionophore to be more selective to Li⁺ than to any of the neurotransmitters studies.