Patch-clamp detection of neurotransmitters in capillary electrophoresis

Science

Volumn 272, Issue 5269, 1996, Pages 1779-1782

  Orwar, Owe ^a   Jardemark, Kent ^b   Jacobson, Ingemar ^b,c   Moscho, Alexander ^a   Fishman, Harvey A ^a   Scheller, Richard H ^a   Zare, Richard N ^a  

^a STANFORD UNIVERSITY   (United States)

^b UNIVERSITY OF GOTHENBURG   (Sweden)

^c ASTRAZENECA R AND D   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

4 AMINOBUTYRIC ACID; DEXTRO ASPARTIC ACID; GLUTAMIC ACID; ION CHANNEL; NEUROTRANSMITTER;

ANIMAL CELL; ARTICLE; CAPILLARY ELECTROPHORESIS; CHANNEL GATING; INTERNEURON; NEUROTRANSMISSION; NONHUMAN; OLFACTORY NERVOUS SYSTEM; PATCH CLAMP; PRIORITY JOURNAL; RAT;

ANIMALIA;

EID: 0030056547     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.272.5269.1779     Document Type: Article

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17. 2+-dependent manner [K. Q. Do et al., J. Neurochem. 46, 779 (1986); M Zollinger et al , ibid. 63, 1133 (1994); M. Kimura et al., Neuroscience 66, 609 (1995)]. Extracellular overflow of NMDA receptor agonists has also been observed during episodes of cerebral ischemia, anoxia, and hypoglycemia [D. W Choi, Neuron 1, 623 (1988); B. Meldrum, in Diversity of Interacting Receptors, L G. Abood and A Lajtha, Eds. (New York Academy of Sciences, New York, 1995), vol. 757, pp. 492-505; H. Hagberg et al., J Cerebral Blood Flow Metab. 5, 413 (1985), M. Sandberg et al., J. Neurochem. 47, 178 (1986); P. Andiné et al., ibid. 57, 230 (1991 ); O. Orwar et al., ibid. 63, 1371 (1994)] Furthermore, unnatural NMDA receptor agonists are important for the etiology of some neurodegenerative diseases [J. W. Olney et al , J. Neuropathol. Exp. Neurol. 34, 167 (1975); P. S. Spencer et al., Science 237, 517 (1987); J. H. Weiss and D W Choi, ibid. 241, 973 (1988)]. Also, the chemical nature of the coagonist acting on NMDA receptors is not firmly established [S Cull-Candy, Curr. Biol. 5, 841 (1995)].
18. 2+-dependent manner [K. Q. Do et al., J. Neurochem. 46, 779 (1986); M Zollinger et al , ibid. 63, 1133 (1994); M. Kimura et al., Neuroscience 66, 609 (1995)]. Extracellular overflow of NMDA receptor agonists has also been observed during episodes of cerebral ischemia, anoxia, and hypoglycemia [D. W Choi, Neuron 1, 623 (1988); B. Meldrum, in Diversity of Interacting Receptors, L G. Abood and A Lajtha, Eds. (New York Academy of Sciences, New York, 1995), vol. 757, pp. 492-505; H. Hagberg et al., J Cerebral Blood Flow Metab. 5, 413 (1985), M. Sandberg et al., J. Neurochem. 47, 178 (1986); P. Andiné et al., ibid. 57, 230 (1991 ); O. Orwar et al., ibid. 63, 1371 (1994)] Furthermore, unnatural NMDA receptor agonists are important for the etiology of some neurodegenerative diseases [J. W. Olney et al , J. Neuropathol. Exp. Neurol. 34, 167 (1975); P. S. Spencer et al., Science 237, 517 (1987); J. H. Weiss and D W Choi, ibid. 241, 973 (1988)]. Also, the chemical nature of the coagonist acting on NMDA receptors is not firmly established [S Cull-Candy, Curr. Biol. 5, 841 (1995)].
19. 2+-dependent manner [K. Q. Do et al., J. Neurochem. 46, 779 (1986); M Zollinger et al , ibid. 63, 1133 (1994); M. Kimura et al., Neuroscience 66, 609 (1995)]. Extracellular overflow of NMDA receptor agonists has also been observed during episodes of cerebral ischemia, anoxia, and hypoglycemia [D. W Choi, Neuron 1, 623 (1988); B. Meldrum, in Diversity of Interacting Receptors, L G. Abood and A Lajtha, Eds. (New York Academy of Sciences, New York, 1995), vol. 757, pp. 492-505; H. Hagberg et al., J Cerebral Blood Flow Metab. 5, 413 (1985), M. Sandberg et al., J. Neurochem. 47, 178 (1986); P. Andiné et al., ibid. 57, 230 (1991 ); O. Orwar et al., ibid. 63, 1371 (1994)] Furthermore, unnatural NMDA receptor agonists are important for the etiology of some neurodegenerative diseases [J. W. Olney et al , J. Neuropathol. Exp. Neurol. 34, 167 (1975); P. S. Spencer et al., Science 237, 517 (1987); J. H. Weiss and D W Choi, ibid. 241, 973 (1988)]. Also, the chemical nature of the coagonist acting on NMDA receptors is not firmly established [S Cull-Candy, Curr. Biol. 5, 841 (1995)].
20. 2+-dependent manner [K. Q. Do et al., J. Neurochem. 46, 779 (1986); M Zollinger et al , ibid. 63, 1133 (1994); M. Kimura et al., Neuroscience 66, 609 (1995)]. Extracellular overflow of NMDA receptor agonists has also been observed during episodes of cerebral ischemia, anoxia, and hypoglycemia [D. W Choi, Neuron 1, 623 (1988); B. Meldrum, in Diversity of Interacting Receptors, L G. Abood and A Lajtha, Eds. (New York Academy of Sciences, New York, 1995), vol. 757, pp. 492-505; H. Hagberg et al., J Cerebral Blood Flow Metab. 5, 413 (1985), M. Sandberg et al., J. Neurochem. 47, 178 (1986); P. Andiné et al., ibid. 57, 230 (1991 ); O. Orwar et al., ibid. 63, 1371 (1994)] Furthermore, unnatural NMDA receptor agonists are important for the etiology of some neurodegenerative diseases [J. W. Olney et al , J. Neuropathol. Exp. Neurol. 34, 167 (1975); P. S. Spencer et al., Science 237, 517 (1987); J. H. Weiss and D W Choi, ibid. 241, 973 (1988)]. Also, the chemical nature of the coagonist acting on NMDA receptors is not firmly established [S Cull-Candy, Curr. Biol. 5, 841 (1995)].
21. 2+-dependent manner [K. Q. Do et al., J. Neurochem. 46, 779 (1986); M Zollinger et al , ibid. 63, 1133 (1994); M. Kimura et al., Neuroscience 66, 609 (1995)]. Extracellular overflow of NMDA receptor agonists has also been observed during episodes of cerebral ischemia, anoxia, and hypoglycemia [D. W Choi, Neuron 1, 623 (1988); B. Meldrum, in Diversity of Interacting Receptors, L G. Abood and A Lajtha, Eds. (New York Academy of Sciences, New York, 1995), vol. 757, pp. 492-505; H. Hagberg et al., J Cerebral Blood Flow Metab. 5, 413 (1985), M. Sandberg et al., J. Neurochem. 47, 178 (1986); P. Andiné et al., ibid. 57, 230 (1991 ); O. Orwar et al., ibid. 63, 1371 (1994)] Furthermore, unnatural NMDA receptor agonists are important for the etiology of some neurodegenerative diseases [J. W. Olney et al , J. Neuropathol. Exp. Neurol. 34, 167 (1975); P. S. Spencer et al., Science 237, 517 (1987); J. H. Weiss and D W Choi, ibid. 241, 973 (1988)]. Also, the chemical nature of the coagonist acting on NMDA receptors is not firmly established [S Cull-Candy, Curr. Biol. 5, 841 (1995)].
22. 2+-dependent manner [K. Q. Do et al., J. Neurochem. 46, 779 (1986); M Zollinger et al , ibid. 63, 1133 (1994); M. Kimura et al., Neuroscience 66, 609 (1995)]. Extracellular overflow of NMDA receptor agonists has also been observed during episodes of cerebral ischemia, anoxia, and hypoglycemia [D. W Choi, Neuron 1, 623 (1988); B. Meldrum, in Diversity of Interacting Receptors, L G. Abood and A Lajtha, Eds. (New York Academy of Sciences, New York, 1995), vol. 757, pp. 492-505; H. Hagberg et al., J Cerebral Blood Flow Metab. 5, 413 (1985), M. Sandberg et al., J. Neurochem. 47, 178 (1986); P. Andiné et al., ibid. 57, 230 (1991 ); O. Orwar et al., ibid. 63, 1371 (1994)] Furthermore, unnatural NMDA receptor agonists are important for the etiology of some neurodegenerative diseases [J. W. Olney et al , J. Neuropathol. Exp. Neurol. 34, 167 (1975); P. S. Spencer et al., Science 237, 517 (1987); J. H. Weiss and D W Choi, ibid. 241, 973 (1988)]. Also, the chemical nature of the coagonist acting on NMDA receptors is not firmly established [S Cull-Candy, Curr. Biol. 5, 841 (1995)].
23. 2+-dependent manner [K. Q. Do et al., J. Neurochem. 46, 779 (1986); M Zollinger et al , ibid. 63, 1133 (1994); M. Kimura et al., Neuroscience 66, 609 (1995)]. Extracellular overflow of NMDA receptor agonists has also been observed during episodes of cerebral ischemia, anoxia, and hypoglycemia [D. W Choi, Neuron 1, 623 (1988); B. Meldrum, in Diversity of Interacting Receptors, L G. Abood and A Lajtha, Eds. (New York Academy of Sciences, New York, 1995), vol. 757, pp. 492-505; H. Hagberg et al., J Cerebral Blood Flow Metab. 5, 413 (1985), M. Sandberg et al., J. Neurochem. 47, 178 (1986); P. Andiné et al., ibid. 57, 230 (1991 ); O. Orwar et al., ibid. 63, 1371 (1994)] Furthermore, unnatural NMDA receptor agonists are important for the etiology of some neurodegenerative diseases [J. W. Olney et al , J. Neuropathol. Exp. Neurol. 34, 167 (1975); P. S. Spencer et al., Science 237, 517 (1987); J. H. Weiss and D W Choi, ibid. 241, 973 (1988)]. Also, the chemical nature of the coagonist acting on NMDA receptors is not firmly established [S Cull-Candy, Curr. Biol. 5, 841 (1995)].
24. 2+-dependent manner [K. Q. Do et al., J. Neurochem. 46, 779 (1986); M Zollinger et al , ibid. 63, 1133 (1994); M. Kimura et al., Neuroscience 66, 609 (1995)]. Extracellular overflow of NMDA receptor agonists has also been observed during episodes of cerebral ischemia, anoxia, and hypoglycemia [D. W Choi, Neuron 1, 623 (1988); B. Meldrum, in Diversity of Interacting Receptors, L G. Abood and A Lajtha, Eds. (New York Academy of Sciences, New York, 1995), vol. 757, pp. 492-505; H. Hagberg et al., J Cerebral Blood Flow Metab. 5, 413 (1985), M. Sandberg et al., J. Neurochem. 47, 178 (1986); P. Andiné et al., ibid. 57, 230 (1991 ); O. Orwar et al., ibid. 63, 1371 (1994)] Furthermore, unnatural NMDA receptor agonists are important for the etiology of some neurodegenerative diseases [J. W. Olney et al , J. Neuropathol. Exp. Neurol. 34, 167 (1975); P. S. Spencer et al., Science 237, 517 (1987); J. H. Weiss and D W Choi, ibid. 241, 973 (1988)]. Also, the chemical nature of the coagonist acting on NMDA receptors is not firmly established [S Cull-Candy, Curr. Biol. 5, 841 (1995)].
25. 2+-dependent manner [K. Q. Do et al., J. Neurochem. 46, 779 (1986); M Zollinger et al , ibid. 63, 1133 (1994); M. Kimura et al., Neuroscience 66, 609 (1995)]. Extracellular overflow of NMDA receptor agonists has also been observed during episodes of cerebral ischemia, anoxia, and hypoglycemia [D. W Choi, Neuron 1, 623 (1988); B. Meldrum, in Diversity of Interacting Receptors, L G. Abood and A Lajtha, Eds. (New York Academy of Sciences, New York, 1995), vol. 757, pp. 492-505; H. Hagberg et al., J Cerebral Blood Flow Metab. 5, 413 (1985), M. Sandberg et al., J. Neurochem. 47, 178 (1986); P. Andiné et al., ibid. 57, 230 (1991 ); O. Orwar et al., ibid. 63, 1371 (1994)] Furthermore, unnatural NMDA receptor agonists are important for the etiology of some neurodegenerative diseases [J. W. Olney et al , J. Neuropathol. Exp. Neurol. 34, 167 (1975); P. S. Spencer et al., Science 237, 517 (1987); J. H. Weiss and D W Choi, ibid. 241, 973 (1988)]. Also, the chemical nature of the coagonist acting on NMDA receptors is not firmly established [S Cull-Candy, Curr. Biol. 5, 841 (1995)].
26. 2+-dependent manner [K. Q. Do et al., J. Neurochem. 46, 779 (1986); M Zollinger et al , ibid. 63, 1133 (1994); M. Kimura et al., Neuroscience 66, 609 (1995)]. Extracellular overflow of NMDA receptor agonists has also been observed during episodes of cerebral ischemia, anoxia, and hypoglycemia [D. W Choi, Neuron 1, 623 (1988); B. Meldrum, in Diversity of Interacting Receptors, L G. Abood and A Lajtha, Eds. (New York Academy of Sciences, New York, 1995), vol. 757, pp. 492-505; H. Hagberg et al., J Cerebral Blood Flow Metab. 5, 413 (1985), M. Sandberg et al., J. Neurochem. 47, 178 (1986); P. Andiné et al., ibid. 57, 230 (1991 ); O. Orwar et al., ibid. 63, 1371 (1994)] Furthermore, unnatural NMDA receptor agonists are important for the etiology of some neurodegenerative diseases [J. W. Olney et al , J. Neuropathol. Exp. Neurol. 34, 167 (1975); P. S. Spencer et al., Science 237, 517 (1987); J. H. Weiss and D W Choi, ibid. 241, 973 (1988)]. Also, the chemical nature of the coagonist acting on NMDA receptors is not firmly established [S Cull-Candy, Curr. Biol. 5, 841 (1995)].
27. 2+-dependent manner [K. Q. Do et al., J. Neurochem. 46, 779 (1986); M Zollinger et al , ibid. 63, 1133 (1994); M. Kimura et al., Neuroscience 66, 609 (1995)]. Extracellular overflow of NMDA receptor agonists has also been observed during episodes of cerebral ischemia, anoxia, and hypoglycemia [D. W Choi, Neuron 1, 623 (1988); B. Meldrum, in Diversity of Interacting Receptors, L G. Abood and A Lajtha, Eds. (New York Academy of Sciences, New York, 1995), vol. 757, pp. 492-505; H. Hagberg et al., J Cerebral Blood Flow Metab. 5, 413 (1985), M. Sandberg et al., J. Neurochem. 47, 178 (1986); P. Andiné et al., ibid. 57, 230 (1991 ); O. Orwar et al., ibid. 63, 1371 (1994)] Furthermore, unnatural NMDA receptor agonists are important for the etiology of some neurodegenerative diseases [J. W. Olney et al , J. Neuropathol. Exp. Neurol. 34, 167 (1975); P. S. Spencer et al., Science 237, 517 (1987); J. H. Weiss and D W Choi, ibid. 241, 973 (1988)]. Also, the chemical nature of the coagonist acting on NMDA receptors is not firmly established [S Cull-Candy, Curr. Biol. 5, 841 (1995)].
28. 2+-dependent manner [K. Q. Do et al., J. Neurochem. 46, 779 (1986); M Zollinger et al , ibid. 63, 1133 (1994); M. Kimura et al., Neuroscience 66, 609 (1995)]. Extracellular overflow of NMDA receptor agonists has also been observed during episodes of cerebral ischemia, anoxia, and hypoglycemia [D. W Choi, Neuron 1, 623 (1988); B. Meldrum, in Diversity of Interacting Receptors, L G. Abood and A Lajtha, Eds. (New York Academy of Sciences, New York, 1995), vol. 757, pp. 492-505; H. Hagberg et al., J Cerebral Blood Flow Metab. 5, 413 (1985), M. Sandberg et al., J. Neurochem. 47, 178 (1986); P. Andiné et al., ibid. 57, 230 (1991 ); O. Orwar et al., ibid. 63, 1371 (1994)] Furthermore, unnatural NMDA receptor agonists are important for the etiology of some neurodegenerative diseases [J. W. Olney et al , J. Neuropathol. Exp. Neurol. 34, 167 (1975); P. S. Spencer et al., Science 237, 517 (1987); J. H. Weiss and D W Choi, ibid. 241, 973 (1988)]. Also, the chemical nature of the coagonist acting on NMDA receptors is not firmly established [S Cull-Candy, Curr. Biol. 5, 841 (1995)].
29. 2+-dependent manner [K. Q. Do et al., J. Neurochem. 46, 779 (1986); M Zollinger et al , ibid. 63, 1133 (1994); M. Kimura et al., Neuroscience 66, 609 (1995)]. Extracellular overflow of NMDA receptor agonists has also been observed during episodes of cerebral ischemia, anoxia, and hypoglycemia [D. W Choi, Neuron 1, 623 (1988); B. Meldrum, in Diversity of Interacting Receptors, L G. Abood and A Lajtha, Eds. (New York Academy of Sciences, New York, 1995), vol. 757, pp. 492-505; H. Hagberg et al., J Cerebral Blood Flow Metab. 5, 413 (1985), M. Sandberg et al., J. Neurochem. 47, 178 (1986); P. Andiné et al., ibid. 57, 230 (1991 ); O. Orwar et al., ibid. 63, 1371 (1994)] Furthermore, unnatural NMDA receptor agonists are important for the etiology of some neurodegenerative diseases [J. W. Olney et al , J. Neuropathol. Exp. Neurol. 34, 167 (1975); P. S. Spencer et al., Science 237, 517 (1987); J. H. Weiss and D W Choi, ibid. 241, 973 (1988)]. Also, the chemical nature of the coagonist acting on NMDA receptors is not firmly established [S Cull-Candy, Curr. Biol. 5, 841 (1995)].
30. 2+-dependent manner [K. Q. Do et al., J. Neurochem. 46, 779 (1986); M Zollinger et al , ibid. 63, 1133 (1994); M. Kimura et al., Neuroscience 66, 609 (1995)]. Extracellular overflow of NMDA receptor agonists has also been observed during episodes of cerebral ischemia, anoxia, and hypoglycemia [D. W Choi, Neuron 1, 623 (1988); B. Meldrum, in Diversity of Interacting Receptors, L G. Abood and A Lajtha, Eds. (New York Academy of Sciences, New York, 1995), vol. 757, pp. 492-505; H. Hagberg et al., J Cerebral Blood Flow Metab. 5, 413 (1985), M. Sandberg et al., J. Neurochem. 47, 178 (1986); P. Andiné et al., ibid. 57, 230 (1991 ); O. Orwar et al., ibid. 63, 1371 (1994)] Furthermore, unnatural NMDA receptor agonists are important for the etiology of some neurodegenerative diseases [J. W. Olney et al , J. Neuropathol. Exp. Neurol. 34, 167 (1975); P. S. Spencer et al., Science 237, 517 (1987); J. H. Weiss and D W Choi, ibid. 241, 973 (1988)]. Also, the chemical nature of the coagonist acting on NMDA receptors is not firmly established [S Cull-Candy, Curr. Biol. 5, 841 (1995)].
31. 2+-dependent manner [K. Q. Do et al., J. Neurochem. 46, 779 (1986); M Zollinger et al , ibid. 63, 1133 (1994); M. Kimura et al., Neuroscience 66, 609 (1995)]. Extracellular overflow of NMDA receptor agonists has also been observed during episodes of cerebral ischemia, anoxia, and hypoglycemia [D. W Choi, Neuron 1, 623 (1988); B. Meldrum, in Diversity of Interacting Receptors, L G. Abood and A Lajtha, Eds. (New York Academy of Sciences, New York, 1995), vol. 757, pp. 492-505; H. Hagberg et al., J Cerebral Blood Flow Metab. 5, 413 (1985), M. Sandberg et al., J. Neurochem. 47, 178 (1986); P. Andiné et al., ibid. 57, 230 (1991 ); O. Orwar et al., ibid. 63, 1371 (1994)] Furthermore, unnatural NMDA receptor agonists are important for the etiology of some neurodegenerative diseases [J. W. Olney et al , J. Neuropathol. Exp. Neurol. 34, 167 (1975); P. S. Spencer et al., Science 237, 517 (1987); J. H. Weiss and D W Choi, ibid. 241, 973 (1988)]. Also, the chemical nature of the coagonist acting on NMDA receptors is not firmly established [S Cull-Candy, Curr. Biol. 5, 841 (1995)].
32. 2+-dependent manner [K. Q. Do et al., J. Neurochem. 46, 779 (1986); M Zollinger et al , ibid. 63, 1133 (1994); M. Kimura et al., Neuroscience 66, 609 (1995)]. Extracellular overflow of NMDA receptor agonists has also been observed during episodes of cerebral ischemia, anoxia, and hypoglycemia [D. W Choi, Neuron 1, 623 (1988); B. Meldrum, in Diversity of Interacting Receptors, L G. Abood and A Lajtha, Eds. (New York Academy of Sciences, New York, 1995), vol. 757, pp. 492-505; H. Hagberg et al., J Cerebral Blood Flow Metab. 5, 413 (1985), M. Sandberg et al., J. Neurochem. 47, 178 (1986); P. Andiné et al., ibid. 57, 230 (1991 ); O. Orwar et al., ibid. 63, 1371 (1994)] Furthermore, unnatural NMDA receptor agonists are important for the etiology of some neurodegenerative diseases [J. W. Olney et al , J. Neuropathol. Exp. Neurol. 34, 167 (1975); P. S. Spencer et al., Science 237, 517 (1987); J. H. Weiss and D W Choi, ibid. 241, 973 (1988)]. Also, the chemical nature of the coagonist acting on NMDA receptors is not firmly established [S Cull-Candy, Curr. Biol. 5, 841 (1995)].
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39. The CE separations were performed in fused-silica capillaries 50 μm in inner diameter (50 cm long) with a high-power supply operated at 12 kV The inlet end of the capillary was positioned 10 cm above the outlet end In the sample injections we placed the capillary inlet in sample solution 20 cm above the outlet end for 10 s The fractured part of the separation capillary was enclosed in a 1-ml polyethylene vial filled with Hepes-saline solution and connected to ground by a Pt wire. We compensated for residual potentials resulting from incomplete grounding by applying a patch-clamp offset potential
40. 2, 11 mM EGTA, and 10 mM Hepes; the pH was adjusted to 7.2 with KOH. Both the outside-out patch-clamp and the whole-cell patch-clamp recording configurations were used, as specified in the text. For outside-out patch-clamp experiments, cells were plated onto cover slips treated with poly-L-lysine and allowed to adhere to the surface for 1 hour before recording. The signals were recorded with a List L/M EPC-7 amplifier, digitized (20 kHz, PCM 2 A/D VCR adapter), and stored on video tape. Data acquisition and initial analysis were performed with programs supplied by J. Dempster, University of Strathclyde, United Kingdom.
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57. Helpful discussions with A. Hamberger, M Sandberg, S G. Weber, M. E. Meyerhoff, and D. T. Chiu and technical assistance from H. Zhao and R. Dadoo are gratefully acknowledged. This work was supported by grants from the National Institute of Mental Health (MH 45423-06) and the National Institute of Drug Abuse (DA 09873-01). The work of O O. was supported by the Swedish Natural Science Research Council (K-PD 10481-303), and that of A.M. was supported by the German Gottlieb Daimler- and Karl Benz-Foundation (2.95.32).