Comparison between sodium-hydrogen ion and lithium-hydrogen ion exchange in human platelets

The membrane-coupled exchange of Li⁺ and/or Na⁺ for H⁺ was studied in human platelets measuring intracellular pH (pH_i) with a fluorescent indicator. A Li⁺-containing medium restored the internal pH of preacidified platelets to their prior pH_i control value. When Na⁺ was replaced by Li⁺, similar steady-state values were attained in this system, although it was transported more slowly. The K_m and V_max were both higher with Na⁺ than with Li⁺. Exchanges of Li⁺ or Na⁺ with H⁺ were both blocked by ethylisopropylamiloride (EIPA) achieving half-maximal inhibition at submicromolar concentrations. The efflux of H⁺ ions exchanged by Li⁺ or Na⁺ was reversible: platelets preloaded with Li⁺ or Na⁺ and resuspended in a choline medium exhibited an influx of H⁺ sensitive to EIPA. Thrombin, an activator of Na⁺/H⁺ exchange, induced a rapid increase in platelet internal pH in the presence of exogenous Li⁺. Thus: (1) Li⁺ can be substituted for Na⁺ in both the forward and the reverse exchange reaction; (2) Li⁺, while having a higher affinity than Na⁺ for the external site of the membrane carrier, has a lower K_m and (3) Li⁺ as well as Na⁺ exchange are activated by thrombin.