CONDUCTING STATES OF A MAMMALIAN SEROTONIN TRANSPORTER

We have studied permeation at a cloned rat 5-HT transporter expressed in Xenopus oocytes. H-35-HT uptake and I-125RTI-55 binding yield a turnover rate of similar to 1/s that does not depend on membrane pote ntial. However, in voltage-clamp experiments, three distinct currents result from 5-HT transporter expression. First, a steady-state, voltag e-dependent transport-associated current is induced by 5-HT applicatio n. Second, a transient inward current is activated by voltage jumps to high negative potentials in the absence of 5-HT and is blocked by 5-H T itself. Third, a small leakage current is observed in the absence of 5-HT. All the observed currents are blocked by inhibitors of 5-HT upt ake but are differentially affected by Na+, Li+, K+, Ba2+, Cs+, Cl-, a nd amiloride. The conducting states of the 5-HT transporter may reflec t the existence of a permeation pathway similar to that of ionic chann els.