Membrane potential drives organic cation transport into teleost renal proximal tubules

The relationship between organic cation uptake and basolateral membrane potential was studied in renal tubules from two marine teleost fish, Southern flounder (Paralicthys lethostigma) and killifish (Fundulus heteroclitis). Carrier-mediated uptake of the model organic cation, tetraethylammonium (TEA), increased when K+ was changed from 2.5 to 0.2 mM and decreased when medium K+ was increased to 20 mM. Uptake was also reduced by the K+ channel blocker barium (1 mM). Furthermore, basolateral membrane potential hyperpolarized 15-25 mV in low-K+ medium and depolarized 30-40 mV in high-K+ medium. Barium also depolarized. Finally, basolateral membrane potential was depolarized in a concentration-dependent manner by addition of 100-500 microM TEA or Darstine. Thus treatments that hyperpolarize the basolateral membrane potential increase carrier-mediated TEA uptake, whereas those that depolarize basolateral membrane potential reduce uptake. Furthermore, organic cation transport into tubular cells involves the net influx of positive charge. Together, these findings support the argument that carrier-mediated organic cation uptake at the basolateral membrane is a potential-driven, electrogenic process.