Conducting states of a mammalian serotonin transporter.
We have studied permeation at a cloned rat 5-HT transporter expressed in Xenopus oocytes. [3H]5-HT uptake and [125I]RTI-55 binding yield a turnover rate of approximately 1/s that does not depend on membrane potential. However, in voltage-clamp experiments, three distinct currents results from 5-HT transporter expression. First, a steady-state, voltage-dependent transport-associated current is induced by 5-HT application. 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-HT 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 uptake but are differentially affected by Na+, Li+, K+, Ba2+, Cs+, Cl-, and amiloride. The conducting states of the 5-HT transporter may reflect the existence of a permeation pathway similar to that of ionic channels.
Mager
S
S
Division of Biology, California Institute of Technology, Pasadena 91125.
Min
C
C
Henry
D J
DJ
Chavkin
C
C
Hoffman
B J
BJ
Davidson
N
N
Lester
H A
HA
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D000838:Anions; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002412:Cations; D003042:Cocaine / Q000031:analogs & derivatives / Q000378:metabolism; D004553:Electric Conductivity; D005260:Female; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D026901:Membrane Transport Proteins; D008670:Metals / Q000494:pharmacology; D009419:Nerve Tissue Proteins; D009865:Oocytes / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology; D050486:Serotonin Plasma Membrane Transport Proteins; D014316:Tritium; D014981:Xenopus
D000838:Anions; D002352:Carrier Proteins; D002412:Cations; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D008670:Metals; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; C493232:Slc6a4 protein, rat; D014316:Tritium; D012701:Serotonin; C069723:2beta-carbomethoxy-3beta-(4-iodophenyl)tropane; D000584:Amiloride; D003042:Cocaine