Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amiloride / pharmacology
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Animals
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Anions
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Carrier Proteins / genetics
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Carrier Proteins / physiology*
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Cations
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Cocaine / analogs & derivatives
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Cocaine / metabolism
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Electric Conductivity
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Female
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / physiology*
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Membrane Potentials / physiology
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Membrane Transport Proteins*
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Metals / pharmacology
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Nerve Tissue Proteins*
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Oocytes / metabolism
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Rats
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Recombinant Proteins
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Serotonin / metabolism
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Serotonin / pharmacology
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Serotonin Plasma Membrane Transport Proteins
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Tritium
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Xenopus
Substances
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Anions
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Carrier Proteins
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Cations
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Membrane Glycoproteins
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Membrane Transport Proteins
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Metals
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Nerve Tissue Proteins
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Recombinant Proteins
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Serotonin Plasma Membrane Transport Proteins
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Slc6a4 protein, rat
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Tritium
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Serotonin
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2beta-carbomethoxy-3beta-(4-iodophenyl)tropane
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Amiloride
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Cocaine