Skip to main content
OSTI.GOVU.S. Department of Energy Office of Scientific and Technical Information
U.S. Department of Energy
Office of Scientific and Technical Information
 

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

Journal Article · · Scientific Reports
 [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)
+ Show Author Affiliations
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.
Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
National Institutes of Health (NIH); USDOE Office of Science (SC)
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
1603561
Journal Information:
Scientific Reports, Journal Name: Scientific Reports Journal Issue: 1 Vol. 9; ISSN 2045-2322
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
English

References (47)

Structure-Activity Relationships in Cholapod Anion Carriers: Enhanced Transmembrane Chloride Transport through Substituent Tuning journal October 2008
Development of Synthetic Membrane Transporters for Anions journal May 2007
A new double-barrelled, ionophore-based microelectrode for chloride ions journal January 1989
Characterization of optimized Na+ and Cl− liquid membranes for use with extracellular, self-referencing microelectrodes journal January 2008
Chloride Dysregulation, Seizures, and Cerebral Edema: A Relationship with Therapeutic Potential journal May 2017
A coordination chemistry dichotomy for icosahedral carborane-based ligands journal July 2011
Efficient, non-toxic anion transport by synthetic carriers in cells and epithelia journal November 2015
Roles of the cation–chloride cotransporters in neurological disease journal September 2008
Simultaneous intracellular chloride and pH measurements using a GFP-based sensor journal June 2010
Chloride anion transporters inhibit growth of methicillin-resistant Staphylococcus aureus (MRSA) in vitro journal January 2016
Synthesis of 9-borafluorene analogues featuring a three-dimensional 1,1′-bis( o -carborane) backbone journal January 2019
On the inhibition of muscle membrane chloride conductance by aromatic carboxylic acids. journal June 1977
The influence of potassium and chloride ions on the membrane potential of single muscle fibres journal October 1959
Continuous direct measurement of intracellular chloride and pH in frog skeletal muscle journal September 1977
Non-passive chloride distribution in mammalian heart muscle: micro-electrode measurement of the intracellular chloride activity. journal October 1979
Intracellular chloride and the mechanism for its accumulation in rat lumbrical muscle. journal April 1989
The action potential-evoked sarcoplasmic reticulum calcium release is impaired in mdx mouse muscle fibres: Calcium release in dystrophic fibres journal May 2004
Local Impermeant Anions Establish the Neuronal Chloride Concentration journal February 2014
Intracellular Measurements of Ion Activities journal June 1983
An improved liquid ion exchanger for chloride ion-selective microelectrodes journal November 1981
Cl(-)-selective microelectrodes: sensitivity to anionic Cl- transport inhibitors journal August 1987
Fabrication and Use of High-Speed, Concentric H + - and Ca 2+ -Selective Microelectrodes Suitable for In Vitro Extracellular Recording journal August 2006
Chloride Accumulation Drives Volume Dynamics Underlying Cell Proliferation and Migration journal February 2009
Bumetanide prevents transient decreases in muscle force in murine hypokalemic periodic paralysis journal February 2013
Regulation of Intracellular Chloride by Cotransporters in Developing Lateral Superior Olive Neurons journal April 1999
Volume-Activated Chloride Currents Contribute to the Resting Conductance and Invasive Migration of Human Glioma Cells journal October 2001
Twenty years of fluorescence imaging of intracellular chloride journal August 2014
Monitoring Ion Activities In and Around Cells Using Ion-Selective Liquid-Membrane Microelectrodes journal January 2013
A new double-barrelled, ionophore-based microelectrode for chloride ions journal January 1989
Chloride-selective electrodes based on mercury organic compounds as neutral carriers journal January 1993
Ion Trapping with Fast-Response Ion-Selective Microelectrodes Enhances Detection of Extracellular Ion Channel Gradients journal February 2009
Mercuracarborand “Anti-Crown Ether”-Based Chloride-Sensitive Liquid/Polymeric Membrane Electrodes journal April 1999
"Anti-crown" chemistry: synthesis of [9]mercuracarborand-3 and the crystal structure of its acetonitrile complexes journal January 1993
The K+/Cl− co-transporter KCC2 renders GABA hyperpolarizing during neuronal maturation journal January 1999
Development of synthetic membrane transporters for anions journal January 2007
Synthetic chloride transporters with the binding mode observed in a ClC chloride channel journal January 2012
Intracellular Cl − as a signaling ion that potently regulates Na + /HCO3 − transporters journal January 2015
Increased Excitability of Acidified Skeletal Muscle journal January 2005
Recovery from acidosis is a robust trigger for loss of force in murine hypokalemic periodic paralysis journal February 2019
An improved liquid ion exchanger for chloride ion-selective microelectrodes journal November 1981
Cl(-)-selective microelectrodes: sensitivity to anionic Cl- transport inhibitors journal August 1987
Intracellular bicarbonate of skeletal muscle under different metabolic states journal January 1976
Bumetanide prevents transient decreases in muscle force in murine hypokalemic periodic paralysis journal February 2013
Potentiometric Selectivity Coefficients of Ion-Selective Electrodes. Part I. Inorganic Cations (Technical Report) journal January 2000
A Synthetic Chloride Channel Restores Chloride Conductance in Human Cystic Fibrosis Epithelial Cells journal April 2012
Regulation of Intracellular Chloride by Cotransporters in Developing Lateral Superior Olive Neurons journal April 1999
Volume-Activated Chloride Currents Contribute to the Resting Conductance and Invasive Migration of Human Glioma Cells journal October 2001

Cited By (1)

Simultaneous Monitoring of pH and Chloride (Cl−) in Brain Slices of Transgenic Mice journal December 2021

Similar Records

Microelectrode study of intracellular pH in frog skin: dependence on serosal Cl/sup -/
Conference · Fri Feb 28 23:00:00 EST 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) · OSTI ID:5320469
Comparative measurements of potassium and chloride with ion-sensitive microelectrodes and x-ray microanalysis in cultured skeletal muscle fibers
Journal Article · Mon Dec 31 23:00:00 EST 1984 · In Vitro Cell. Develop. Biol.; (United States) · OSTI ID:5850267
Microelectrodes in microbial ecology
Journal Article · Tue Mar 14 23:00:00 EST 1989 · Analytical Chemistry; (USA) · OSTI ID:5191664

Related Subjects

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
electrophysiology
ion transport
neurophysiology
sensors and probes