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:
-
- Univ. of California, Los Angeles, CA (United States). David Geffen School of Medicine
- Univ. of California, Los Angeles, CA (United States)
- Publication Date:
- Research Org.:
- Lawrence Berkeley National Laboratory (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. 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. 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 = {Wed Dec 11 00:00:00 EST 2019},
month = {Wed Dec 11 00:00:00 EST 2019}
}
Web of Science
Works referenced in this record:
The action potential-evoked sarcoplasmic reticulum calcium release is impaired in mdx mouse muscle fibres: Calcium release in dystrophic fibres
journal, May 2004
- Woods, Christopher E.; Novo, David; DiFranco, Marino
- The Journal of Physiology, Vol. 557, Issue 1
Chloride Accumulation Drives Volume Dynamics Underlying Cell Proliferation and Migration
journal, February 2009
- Habela, Christa W.; Ernest, Nola Jean; Swindall, Amanda F.
- Journal of Neurophysiology, Vol. 101, Issue 2
Intracellular Cl − as a signaling ion that potently regulates Na + /HCO3 − transporters
journal, January 2015
- Shcheynikov, Nikolay; Son, Aran; Hong, Jeong Hee
- Proceedings of the National Academy of Sciences, Vol. 112, Issue 3
Roles of the cation–chloride cotransporters in neurological disease
journal, September 2008
- Kahle, Kristopher T.; Staley, Kevin J.; Nahed, Brian V.
- Nature Clinical Practice Neurology, Vol. 4, Issue 9
Monitoring Ion Activities In and Around Cells Using Ion-Selective Liquid-Membrane Microelectrodes
journal, January 2013
- Lee, Seong-Ki; Boron, Walter; Parker, Mark
- Sensors, Vol. 13, Issue 1
Potentiometric Selectivity Coefficients of Ion-Selective Electrodes. Part I. Inorganic Cations (Technical Report)
journal, January 2000
- Umezawa, Yoshio; Bühlmann, Philippe; Umezawa, Kayoko
- Pure and Applied Chemistry, Vol. 72, Issue 10
Recovery from acidosis is a robust trigger for loss of force in murine hypokalemic periodic paralysis
journal, February 2019
- Mi, Wentao; Wu, Fenfen; Quinonez, Marbella
- Journal of General Physiology, Vol. 151, Issue 4
"Anti-crown" chemistry: synthesis of [9]mercuracarborand-3 and the crystal structure of its acetonitrile complexes
journal, January 1993
- Yang, Xiaoguang; Zheng, Zhiping; Knobler, Carolyn B.
- Journal of the American Chemical Society, Vol. 115, Issue 1
Structure-Activity Relationships in Cholapod Anion Carriers: Enhanced Transmembrane Chloride Transport through Substituent Tuning
journal, October 2008
- McNally, Beth A.; Koulov, Atanas V.; Lambert, Timothy N.
- Chemistry - A European Journal, Vol. 14, Issue 31
Non-passive chloride distribution in mammalian heart muscle: micro-electrode measurement of the intracellular chloride activity.
journal, October 1979
- Vaughan-Jones, R. D.
- The Journal of Physiology, Vol. 295, Issue 1
Characterization of optimized Na+ and Cl− liquid membranes for use with extracellular, self-referencing microelectrodes
journal, January 2008
- Messerli, Mark A.; Kurtz, Ira; Smith, Peter J. S.
- Analytical and Bioanalytical Chemistry, Vol. 390, Issue 5
A Synthetic Chloride Channel Restores Chloride Conductance in Human Cystic Fibrosis Epithelial Cells
journal, April 2012
- Shen, Bing; Li, Xiang; Wang, Fei
- PLoS ONE, Vol. 7, Issue 4
Local Impermeant Anions Establish the Neuronal Chloride Concentration
journal, February 2014
- Glykys, J.; Dzhala, V.; Egawa, K.
- Science, Vol. 343, Issue 6171
Chloride anion transporters inhibit growth of methicillin-resistant Staphylococcus aureus (MRSA) in vitro
journal, January 2016
- Share, Andrew I.; Patel, Khushali; Nativi, Cristina
- Chemical Communications, Vol. 52, Issue 48
Continuous direct measurement of intracellular chloride and pH in frog skeletal muscle
journal, September 1977
- Bolton, T. B.; Vaughan-Jones, R. D.
- The Journal of Physiology, Vol. 270, Issue 3
Mercuracarborand “Anti-Crown Ether”-Based Chloride-Sensitive Liquid/Polymeric Membrane Electrodes
journal, April 1999
- Badr, Ibrahim H. A.; Diaz, Martin; Hawthorne, M. Frederick
- Analytical Chemistry, Vol. 71, Issue 7
Efficient, non-toxic anion transport by synthetic carriers in cells and epithelia
journal, November 2015
- Li, Hongyu; Valkenier, Hennie; Judd, Luke W.
- Nature Chemistry, Vol. 8, Issue 1
Chloride Dysregulation, Seizures, and Cerebral Edema: A Relationship with Therapeutic Potential
journal, May 2017
- Glykys, Joseph; Dzhala, Volodymyr; Egawa, Kiyoshi
- Trends in Neurosciences, Vol. 40, Issue 5
Development of synthetic membrane transporters for anions
journal, January 2007
- Davis, Anthony P.; Sheppard, David N.; Smith, Bradley D.
- Chem. Soc. Rev., Vol. 36, Issue 2
On the inhibition of muscle membrane chloride conductance by aromatic carboxylic acids.
journal, June 1977
- Palade, P. T.; Barchi, R. L.
- The Journal of General Physiology, Vol. 69, Issue 6
Intracellular bicarbonate of skeletal muscle under different metabolic states
journal, January 1976
- Khuri, Rn; Agulian, Sk; Bogharian, Kk
- American Journal of Physiology-Legacy Content, Vol. 230, Issue 1
Synthetic chloride transporters with the binding mode observed in a ClC chloride channel
journal, January 2012
- Choi, Ye Rin; Chae, Min Kyung; Kim, Dongwook
- Chemical Communications, Vol. 48, Issue 83
Increased Excitability of Acidified Skeletal Muscle
journal, January 2005
- Pedersen, Thomas H.; de Paoli, Frank; Nielsen, Ole B.
- Journal of General Physiology, Vol. 125, Issue 2
The K+/Cl− co-transporter KCC2 renders GABA hyperpolarizing during neuronal maturation
journal, January 1999
- Rivera, Claudio; Voipio, Juha; Payne, John A.
- Nature, Vol. 397, Issue 6716
Simultaneous intracellular chloride and pH measurements using a GFP-based sensor
journal, June 2010
- Arosio, Daniele; Ricci, Fernanda; Marchetti, Laura
- Nature Methods, Vol. 7, Issue 7
Synthesis of 9-borafluorene analogues featuring a three-dimensional 1,1′-bis( o -carborane) backbone
journal, January 2019
- Yruegas, Sam; Axtell, Jonathan C.; Kirlikovali, Kent O.
- Chemical Communications, Vol. 55, Issue 20
Twenty years of fluorescence imaging of intracellular chloride
journal, August 2014
- Arosio, Daniele; Ratto, Gian Michele
- Frontiers in Cellular Neuroscience, Vol. 8
A coordination chemistry dichotomy for icosahedral carborane-based ligands
journal, July 2011
- Spokoyny, Alexander M.; Machan, Charles W.; Clingerman, Daniel J.
- Nature Chemistry, Vol. 3, Issue 8
Intracellular chloride and the mechanism for its accumulation in rat lumbrical muscle.
journal, April 1989
- Aickin, C. C.; Betz, W. J.; Harris, G. L.
- The Journal of Physiology, Vol. 411, Issue 1
Ion Trapping with Fast-Response Ion-Selective Microelectrodes Enhances Detection of Extracellular Ion Channel Gradients
journal, February 2009
- Messerli, Mark A.; Collis, Leon P.; Smith, Peter J. S.
- Biophysical Journal, Vol. 96, Issue 4
Fabrication and Use of High-Speed, Concentric H + - and Ca 2+ -Selective Microelectrodes Suitable for In Vitro Extracellular Recording
journal, August 2006
- Fedirko, Nataliya; Svichar, Nataliya; Chesler, Mitchell
- Journal of Neurophysiology, Vol. 96, Issue 2
The influence of potassium and chloride ions on the membrane potential of single muscle fibres
journal, October 1959
- Hodgkin, A. L.; Horowicz, P.
- The Journal of Physiology, Vol. 148, Issue 1
Chloride-selective electrodes based on mercury organic compounds as neutral carriers
journal, January 1993
- Rothmaier, Markus; Simon, Wilhelm
- Analytica Chimica Acta, Vol. 271, Issue 1
Intracellular Measurements of Ion Activities
journal, June 1983
- Tsien, Roger Y.
- Annual Review of Biophysics and Bioengineering, Vol. 12, Issue 1
Structure-Activity Relationships in Cholapod Anion Carriers: Enhanced Transmembrane Chloride Transport through Substituent Tuning
journal, October 2008
- McNally, Beth A.; Koulov, Atanas V.; Lambert, Timothy N.
- Chemistry - A European Journal, Vol. 14, Issue 31
Development of Synthetic Membrane Transporters for Anions
journal, May 2007
- Davis, Anthony P.; Sheppard, David N.; Smith, Bradley D.
- ChemInform, Vol. 38, Issue 21
A new double-barrelled, ionophore-based microelectrode for chloride ions
journal, January 1989
- Kondo, Y.; B�hrer, T.; Fr�mter, E.
- Pfl�gers Archiv European Journal of Physiology, Vol. 414, Issue 6
Characterization of optimized Na+ and Cl− liquid membranes for use with extracellular, self-referencing microelectrodes
journal, January 2008
- Messerli, Mark A.; Kurtz, Ira; Smith, Peter J. S.
- Analytical and Bioanalytical Chemistry, Vol. 390, Issue 5
Chloride Dysregulation, Seizures, and Cerebral Edema: A Relationship with Therapeutic Potential
journal, May 2017
- Glykys, Joseph; Dzhala, Volodymyr; Egawa, Kiyoshi
- Trends in Neurosciences, Vol. 40, Issue 5
A coordination chemistry dichotomy for icosahedral carborane-based ligands
journal, July 2011
- Spokoyny, Alexander M.; Machan, Charles W.; Clingerman, Daniel J.
- Nature Chemistry, Vol. 3, Issue 8
Efficient, non-toxic anion transport by synthetic carriers in cells and epithelia
journal, November 2015
- Li, Hongyu; Valkenier, Hennie; Judd, Luke W.
- Nature Chemistry, Vol. 8, Issue 1
Roles of the cation–chloride cotransporters in neurological disease
journal, September 2008
- Kahle, Kristopher T.; Staley, Kevin J.; Nahed, Brian V.
- Nature Clinical Practice Neurology, Vol. 4, Issue 9
Simultaneous intracellular chloride and pH measurements using a GFP-based sensor
journal, June 2010
- Arosio, Daniele; Ricci, Fernanda; Marchetti, Laura
- Nature Methods, Vol. 7, Issue 7
Chloride anion transporters inhibit growth of methicillin-resistant Staphylococcus aureus (MRSA) in vitro
journal, January 2016
- Share, Andrew I.; Patel, Khushali; Nativi, Cristina
- Chemical Communications, Vol. 52, Issue 48
Synthesis of 9-borafluorene analogues featuring a three-dimensional 1,1′-bis( o -carborane) backbone
journal, January 2019
- Yruegas, Sam; Axtell, Jonathan C.; Kirlikovali, Kent O.
- Chemical Communications, Vol. 55, Issue 20
On the inhibition of muscle membrane chloride conductance by aromatic carboxylic acids.
journal, June 1977
- Palade, P. T.; Barchi, R. L.
- The Journal of General Physiology, Vol. 69, Issue 6
The influence of potassium and chloride ions on the membrane potential of single muscle fibres
journal, October 1959
- Hodgkin, A. L.; Horowicz, P.
- The Journal of Physiology, Vol. 148, Issue 1
Continuous direct measurement of intracellular chloride and pH in frog skeletal muscle
journal, September 1977
- Bolton, T. B.; Vaughan-Jones, R. D.
- The Journal of Physiology, Vol. 270, Issue 3
Non-passive chloride distribution in mammalian heart muscle: micro-electrode measurement of the intracellular chloride activity.
journal, October 1979
- Vaughan-Jones, R. D.
- The Journal of Physiology, Vol. 295, Issue 1
Intracellular chloride and the mechanism for its accumulation in rat lumbrical muscle.
journal, April 1989
- Aickin, C. C.; Betz, W. J.; Harris, G. L.
- The Journal of Physiology, Vol. 411, Issue 1
The action potential-evoked sarcoplasmic reticulum calcium release is impaired in mdx mouse muscle fibres: Calcium release in dystrophic fibres
journal, May 2004
- Woods, Christopher E.; Novo, David; DiFranco, Marino
- The Journal of Physiology, Vol. 557, Issue 1
Local Impermeant Anions Establish the Neuronal Chloride Concentration
journal, February 2014
- Glykys, J.; Dzhala, V.; Egawa, K.
- Science, Vol. 343, Issue 6171
Intracellular Measurements of Ion Activities
journal, June 1983
- Tsien, Roger Y.
- Annual Review of Biophysics and Bioengineering, Vol. 12, Issue 1
An improved liquid ion exchanger for chloride ion-selective microelectrodes
journal, November 1981
- Baumgarten, C. M.
- American Journal of Physiology-Cell Physiology, Vol. 241, Issue 5
Cl(-)-selective microelectrodes: sensitivity to anionic Cl- transport inhibitors
journal, August 1987
- Chao, A. C.; Armstrong, W. M.
- American Journal of Physiology-Cell Physiology, Vol. 253, Issue 2
Fabrication and Use of High-Speed, Concentric H + - and Ca 2+ -Selective Microelectrodes Suitable for In Vitro Extracellular Recording
journal, August 2006
- Fedirko, Nataliya; Svichar, Nataliya; Chesler, Mitchell
- Journal of Neurophysiology, Vol. 96, Issue 2
Chloride Accumulation Drives Volume Dynamics Underlying Cell Proliferation and Migration
journal, February 2009
- Habela, Christa W.; Ernest, Nola Jean; Swindall, Amanda F.
- Journal of Neurophysiology, Vol. 101, Issue 2
Bumetanide prevents transient decreases in muscle force in murine hypokalemic periodic paralysis
journal, February 2013
- Wu, F.; Mi, W.; Cannon, S. C.
- Neurology, Vol. 80, Issue 12
Regulation of Intracellular Chloride by Cotransporters in Developing Lateral Superior Olive Neurons
journal, April 1999
- Kakazu, Yasuhiro; Akaike, Norio; Komiyama, Soutaro
- The Journal of Neuroscience, Vol. 19, Issue 8
Volume-Activated Chloride Currents Contribute to the Resting Conductance and Invasive Migration of Human Glioma Cells
journal, October 2001
- Ransom, Christopher B.; O'Neal, Jeffrey T.; Sontheimer, Harald
- The Journal of Neuroscience, Vol. 21, Issue 19
Twenty years of fluorescence imaging of intracellular chloride
journal, August 2014
- Arosio, Daniele; Ratto, Gian Michele
- Frontiers in Cellular Neuroscience, Vol. 8
Monitoring Ion Activities In and Around Cells Using Ion-Selective Liquid-Membrane Microelectrodes
journal, January 2013
- Lee, Seong-Ki; Boron, Walter; Parker, Mark
- Sensors, Vol. 13, Issue 1
Works referencing / citing this record:
Simultaneous Monitoring of pH and Chloride (Cl−) in Brain Slices of Transgenic Mice
journal, December 2021
- Ponomareva, Daria; Petukhova, Elena; Bregestovski, Piotr
- International Journal of Molecular Sciences, Vol. 22, Issue 24