skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Stimulation of TRPC5 cationic channels by low micromolar concentrations of lead ions (Pb{sup 2+})

Abstract

Lead toxicity is long-recognised but continues to be a major public health problem. Its effects are wide-ranging and include induction of hyper-anxiety states. In general it is thought to act by interfering with Ca{sup 2+} signalling but specific targets are not clearly identified. Transient receptor potential canonical 5 (TRPC5) is a Ca{sup 2+}-permeable ion channel that is linked positively to innate fear responses and unusual amongst ion channels in being stimulated by trivalent lanthanides, which include gadolinium. Here we show investigation of the effect of lead, which is a divalent ion (Pb{sup 2+}). Intracellular Ca{sup 2+} and whole-cell patch-clamp recordings were performed on HEK 293 cells conditionally over-expressing TRPC5 or other TRP channels. Extracellular application of Pb{sup 2+} stimulated TRPC5 at concentrations greater than 1 {mu}M. Control cells without TRPC5 showed little or no response to Pb{sup 2+} and expression of other TRP channels (TRPM2 or TRPM3) revealed partial inhibition by 10 {mu}M Pb{sup 2+}. The stimulatory effect on TRPC5 depended on an extracellular residue (E543) near the ion pore: similar to gadolinium action, E543Q TRPC5 was resistant to Pb{sup 2+} but showed normal stimulation by the receptor agonist sphingosine-1-phosphate. The study shows that Pb{sup 2+} is a relatively potentmore » stimulator of the TRPC5 channel, generating the hypothesis that a function of the channel is to sense metal ion poisoning.« less

Authors:
 [1]
  1. Multidisciplinary Cardiovascular Research Centre and Institute of Membrane and Systems Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT (United Kingdom)
Publication Date:
OSTI Identifier:
22202389
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 393; Journal Issue: 1; Other Information: Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CALCIUM IONS; CONCENTRATION RATIO; GADOLINIUM; INHIBITION; LEAD IONS; PHOSPHATES; POISONING; PUBLIC HEALTH; RECEPTORS; RESIDUES; STIMULATION; TOXICITY

Citation Formats

Sukumar, Piruthivi, and Beech, David J., E-mail: d.j.beech@leeds.ac.uk. Stimulation of TRPC5 cationic channels by low micromolar concentrations of lead ions (Pb{sup 2+}). United States: N. p., 2010. Web. doi:10.1016/J.BBRC.2010.01.074.
Sukumar, Piruthivi, & Beech, David J., E-mail: d.j.beech@leeds.ac.uk. Stimulation of TRPC5 cationic channels by low micromolar concentrations of lead ions (Pb{sup 2+}). United States. https://doi.org/10.1016/J.BBRC.2010.01.074
Sukumar, Piruthivi, and Beech, David J., E-mail: d.j.beech@leeds.ac.uk. 2010. "Stimulation of TRPC5 cationic channels by low micromolar concentrations of lead ions (Pb{sup 2+})". United States. https://doi.org/10.1016/J.BBRC.2010.01.074.
@article{osti_22202389,
title = {Stimulation of TRPC5 cationic channels by low micromolar concentrations of lead ions (Pb{sup 2+})},
author = {Sukumar, Piruthivi and Beech, David J., E-mail: d.j.beech@leeds.ac.uk},
abstractNote = {Lead toxicity is long-recognised but continues to be a major public health problem. Its effects are wide-ranging and include induction of hyper-anxiety states. In general it is thought to act by interfering with Ca{sup 2+} signalling but specific targets are not clearly identified. Transient receptor potential canonical 5 (TRPC5) is a Ca{sup 2+}-permeable ion channel that is linked positively to innate fear responses and unusual amongst ion channels in being stimulated by trivalent lanthanides, which include gadolinium. Here we show investigation of the effect of lead, which is a divalent ion (Pb{sup 2+}). Intracellular Ca{sup 2+} and whole-cell patch-clamp recordings were performed on HEK 293 cells conditionally over-expressing TRPC5 or other TRP channels. Extracellular application of Pb{sup 2+} stimulated TRPC5 at concentrations greater than 1 {mu}M. Control cells without TRPC5 showed little or no response to Pb{sup 2+} and expression of other TRP channels (TRPM2 or TRPM3) revealed partial inhibition by 10 {mu}M Pb{sup 2+}. The stimulatory effect on TRPC5 depended on an extracellular residue (E543) near the ion pore: similar to gadolinium action, E543Q TRPC5 was resistant to Pb{sup 2+} but showed normal stimulation by the receptor agonist sphingosine-1-phosphate. The study shows that Pb{sup 2+} is a relatively potent stimulator of the TRPC5 channel, generating the hypothesis that a function of the channel is to sense metal ion poisoning.},
doi = {10.1016/J.BBRC.2010.01.074},
url = {https://www.osti.gov/biblio/22202389}, journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 1,
volume = 393,
place = {United States},
year = {Fri Feb 26 00:00:00 EST 2010},
month = {Fri Feb 26 00:00:00 EST 2010}
}