Effects of the abused inhalant toluene on ethanol-sensitive potassium channels expressed in oocytes

Angelo M. Del Re, Alejandro Dopico, John J. Woodward

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Toluene (methylbenzene) is representative of a class of industrial solvents that are voluntarily inhaled as drugs of abuse. Previous data from this laboratory and others have shown that these compounds alter the function of a variety of ion channels including ligand-gated channels activated by ATP, acetylcholine, GABA, glutamate and serotonin, as well as voltage-dependent sodium and calcium channels. It is less clear what effects toluene may have on potassium channels that act to reduce the excitability of most cells. Previous studies have shown that ethanol potentiates the function of both the large conductance, calcium-activated potassium channel (BK) and specific members of the G-protein-coupled inwardly rectifying potassium channels (GirKs). Since toluene and other abused inhalants share many behavioral effects with ethanol, it was hypothesized that toluene would also enhance the function of these channels. This hypothesis was tested using two-electrode voltage-clamp electrophysiology to measure the activity of BK and GirK potassium channel currents expressed in Xenopus laevis oocytes. As reported previously, ethanol potentiated currents in oocytes expressing either BK or GirK2 channels. In contrast, toluene caused a concentration-dependent inhibition of BK channel currents with 3 mM producing approximately 50% inhibition of control currents. Currents in oocytes injected with GirK2 mRNA were also inhibited by toluene while those expressing GirK1/2 and 1/4 channels were minimally affected. In oocytes co-injected with mRNA for GirK2 and the mGluR1a metabotropic receptor, exposure to glutamate potentiated currents evoked by a high-potassium solution. Toluene inhibited these glutamate-activated currents to approximately the same degree as those induced under basal conditions. The results of these studies show that toluene has effects on BK and GirK channels that are opposite to those of ethanol, suggesting that these channels are unlikely to underlie behaviors that these two drugs of abuse share.

Original languageEnglish (US)
Pages (from-to)75-82
Number of pages8
JournalBrain Research
Volume1087
Issue number1
DOIs
StatePublished - May 4 2006

Fingerprint

Potassium Channels
Toluene
Oocytes
Ethanol
Large-Conductance Calcium-Activated Potassium Channels
Glutamic Acid
Street Drugs
G Protein-Coupled Inwardly-Rectifying Potassium Channels
Ligand-Gated Ion Channels
Messenger RNA
Sodium Channels
Electrophysiology
Xenopus laevis
Calcium Channels
Ion Channels
gamma-Aminobutyric Acid
Acetylcholine
Serotonin
Potassium
Electrodes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

Cite this

Effects of the abused inhalant toluene on ethanol-sensitive potassium channels expressed in oocytes. / Del Re, Angelo M.; Dopico, Alejandro; Woodward, John J.

In: Brain Research, Vol. 1087, No. 1, 04.05.2006, p. 75-82.

Research output: Contribution to journalArticle

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abstract = "Toluene (methylbenzene) is representative of a class of industrial solvents that are voluntarily inhaled as drugs of abuse. Previous data from this laboratory and others have shown that these compounds alter the function of a variety of ion channels including ligand-gated channels activated by ATP, acetylcholine, GABA, glutamate and serotonin, as well as voltage-dependent sodium and calcium channels. It is less clear what effects toluene may have on potassium channels that act to reduce the excitability of most cells. Previous studies have shown that ethanol potentiates the function of both the large conductance, calcium-activated potassium channel (BK) and specific members of the G-protein-coupled inwardly rectifying potassium channels (GirKs). Since toluene and other abused inhalants share many behavioral effects with ethanol, it was hypothesized that toluene would also enhance the function of these channels. This hypothesis was tested using two-electrode voltage-clamp electrophysiology to measure the activity of BK and GirK potassium channel currents expressed in Xenopus laevis oocytes. As reported previously, ethanol potentiated currents in oocytes expressing either BK or GirK2 channels. In contrast, toluene caused a concentration-dependent inhibition of BK channel currents with 3 mM producing approximately 50{\%} inhibition of control currents. Currents in oocytes injected with GirK2 mRNA were also inhibited by toluene while those expressing GirK1/2 and 1/4 channels were minimally affected. In oocytes co-injected with mRNA for GirK2 and the mGluR1a metabotropic receptor, exposure to glutamate potentiated currents evoked by a high-potassium solution. Toluene inhibited these glutamate-activated currents to approximately the same degree as those induced under basal conditions. The results of these studies show that toluene has effects on BK and GirK channels that are opposite to those of ethanol, suggesting that these channels are unlikely to underlie behaviors that these two drugs of abuse share.",
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