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Title: A highly-selective chloride microelectrode based on a mercuracarborand anion carrier

Abstract

The chloride gradient plays an important role in regulating cell volume, membrane potential, pH, secretion, and the reversal potential of inhibitory glycine and GABAA receptors. Measurement of intracellular chloride activity, $$a^i_{Cl}$$, using liquid membrane ion-selective microelectrodes (ISM), however, has been limited by the physiochemical properties of Cl- ionophores which have caused poor stability, drift, sluggish response times, and interference from other biologically relevant anions. Most importantly, intracellular $$HCO^-_3$$ may be up to 4 times more abundant than Cl- (e.g. skeletal muscle) which places severe constraints on the required selectivity of a Cl- - sensing ISM. Previously, a sensitive and highly-selective Cl- sensor was developed in a polymeric membrane electrode using a trinuclear Hg(II) complex containing carborane-based ligands, [9]-mercuracarborand-3, or MC3 for short. Here, we have adapted the use of the MC3 anion carrier in a liquid membrane ion-selective microelectrode and show the MC3-ISM has a linear Nernstian response over a wide range of aCl (0.1 mM to 100 mM), is highly selective for Cl- over other biological anions or inhibitors of Cl- transport, and has a 10% to 90% settling  time of 3 sec. Importantly, over the physiological range of aCl (1 mM to 100 mM) the potentiometric response of the MC3-ISM is insensitive to $$HCO^-_3$$ or changes in pH. Finally, we demonstrate the biological application of an MC3-ISM by measuring intracellular aCl, and the response to an external Cl-free challenge, for an isolated skeletal muscle fiber.

Authors:
 [1];  [1];  [2];  [2];  [1]
  1. Univ. of California, Los Angeles, CA (United States). David Geffen School of Medicine
  2. Univ. of California, Los Angeles, CA (United States)
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC); National Institutes of Health (NIH)
OSTI Identifier:
1603561
Grant/Contract Number:  
AC02-05CH11231; AR63182; AR42703; RG-381149; R21-AR067422
Resource Type:
Accepted Manuscript
Journal Name:
Scientific Reports
Additional Journal Information:
Journal Volume: 9; Journal Issue: 1; Journal ID: ISSN 2045-2322
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; electrophysiology; ion transport; neurophysiology; sensors and probes

Citation Formats

DiFranco, Marino, Quinonez, Marbella, Dziedzic, Rafal M., Spokoyny, Alexander M., and Cannon, Stephen C. A highly-selective chloride microelectrode based on a mercuracarborand anion carrier. United States: N. p., 2019. Web. doi:10.1038/s41598-019-54885-6.
DiFranco, Marino, Quinonez, Marbella, Dziedzic, Rafal M., Spokoyny, Alexander M., & Cannon, Stephen C. A highly-selective chloride microelectrode based on a mercuracarborand anion carrier. United States. doi:https://doi.org/10.1038/s41598-019-54885-6
DiFranco, Marino, Quinonez, Marbella, Dziedzic, Rafal M., Spokoyny, Alexander M., and Cannon, Stephen C. Wed . "A highly-selective chloride microelectrode based on a mercuracarborand anion carrier". United States. doi:https://doi.org/10.1038/s41598-019-54885-6. https://www.osti.gov/servlets/purl/1603561.
@article{osti_1603561,
title = {A highly-selective chloride microelectrode based on a mercuracarborand anion carrier},
author = {DiFranco, Marino and Quinonez, Marbella and Dziedzic, Rafal M. and Spokoyny, Alexander M. and Cannon, Stephen C.},
abstractNote = {The chloride gradient plays an important role in regulating cell volume, membrane potential, pH, secretion, and the reversal potential of inhibitory glycine and GABAA receptors. Measurement of intracellular chloride activity, $a^i_{Cl}$, using liquid membrane ion-selective microelectrodes (ISM), however, has been limited by the physiochemical properties of Cl- ionophores which have caused poor stability, drift, sluggish response times, and interference from other biologically relevant anions. Most importantly, intracellular $HCO^-_3$ may be up to 4 times more abundant than Cl- (e.g. skeletal muscle) which places severe constraints on the required selectivity of a Cl- - sensing ISM. Previously, a sensitive and highly-selective Cl- sensor was developed in a polymeric membrane electrode using a trinuclear Hg(II) complex containing carborane-based ligands, [9]-mercuracarborand-3, or MC3 for short. Here, we have adapted the use of the MC3 anion carrier in a liquid membrane ion-selective microelectrode and show the MC3-ISM has a linear Nernstian response over a wide range of aCl (0.1 mM to 100 mM), is highly selective for Cl- over other biological anions or inhibitors of Cl- transport, and has a 10% to 90% settling  time of 3 sec. Importantly, over the physiological range of aCl (1 mM to 100 mM) the potentiometric response of the MC3-ISM is insensitive to $HCO^-_3$ or changes in pH. Finally, we demonstrate the biological application of an MC3-ISM by measuring intracellular aCl, and the response to an external Cl-free challenge, for an isolated skeletal muscle fiber.},
doi = {10.1038/s41598-019-54885-6},
journal = {Scientific Reports},
number = 1,
volume = 9,
place = {United States},
year = {2019},
month = {12}
}

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