Multiple-conductance channels activated by excitatory amino acids in cerebellar neurons

ABSTRACT In the mammalian central nervous system amino acids such as L-glutamate and L-aspartate are thought to act as fast synaptic transmitters1,2. It has been suggested that at least

three pharmacologically-distinguishable types of glutamate receptor occur in central neurons and that these are selectively activated by the glutamate analogues _N_-methyl-D-aspartate

(NMDA), quisqualate and kainate3–5. These three receptor types would be expected to open ion channels with different conductances. Hence if agonists produce similar channel conductances this

would suggest they are acting on the same receptor6,7. Another possibility is suggested by experiments on spinal neurons8, where GABA (γ-amino butyric acid) and glycine appear to open

different sub-conductance levels of one class of channel while acting on different receptors. By analogy, several types of glutamate receptor could also be linked to a single type of channel

with several sub-conductance states. We have examined these possibilities in cerebellar neurons by analysing the single-channel currents9 activated by L-glutamate, L-aspartate, NMDA,

quisqualate and kainate in excised membrane patches. All of these agonists are capable of opening channels with at least five different conductance levels, the largest being about 45–50 pS.

NMDA predominantly activated conductance levels above 30 pS while quisqualate and kainate mainly activated ones below 20 pS. The presence of clear transitions between levels favours the idea

that the five main levels are all sub-states of the same type of channel. Access through your institution Buy or subscribe This is a preview of subscription content, access via your

institution ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 51 print issues and online access $199.00 per year only $3.90 per issue Learn more Buy this

article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in

* Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS SUBCELLULAR PATCH-CLAMP TECHNIQUES FOR SINGLE-BOUTON STIMULATION

AND SIMULTANEOUS PRE- AND POSTSYNAPTIC RECORDING AT CORTICAL SYNAPSES Article 14 May 2021 KINETIC FINGERPRINTING OF METABOTROPIC GLUTAMATE RECEPTORS Article Open access 27 January 2023

CA2+-ACTIVATED KCA3.1 POTASSIUM CHANNELS CONTRIBUTE TO THE SLOW AFTERHYPERPOLARIZATION IN L5 NEOCORTICAL PYRAMIDAL NEURONS Article Open access 02 September 2020 REFERENCES * Curtis, D. R.

& Johnston, G. A. R. _Ergebn. Physiol._ 69, 97–188 (1974). CAS  PubMed  Google Scholar  * Krnjevic, K. _Physiol. Rev._ 54, 418–540 (1974). Article  CAS  Google Scholar  * Watkins, J. C.

& Evans, R. H. _A. Rev. Pharmac. Toxicol._ 21, 165–204 (1981). Article  CAS  Google Scholar  * Foster, A. C. & Fagg, G. E. _Brain Res. Rev._ 7, 103–164 (1984). Article  CAS  Google

Scholar  * Mayer, M. L. & Westbrook, G. L. _J. Physiol., Lond._ 384, 29–53 (1984). Article  Google Scholar  * Cull-Candy, S. G., Miledi, R. & Parker, I. _J. Physiol., Lond._ 321,

195–210 (1981). Article  CAS  PubMed  PubMed Central  Google Scholar  * Gardner, P., Ogden, D. C. & Colquhoun, D. _Nature_ 309, 160–162 (1984). Article  ADS  CAS  PubMed  Google Scholar

  * Hamill, O. P., Bormann, J. & Sakmann, B. _Nature_ 305, 805–808 (1983). Article  ADS  CAS  PubMed  Google Scholar  * Hamill, O. P., Marty, A., Neher, E., Sakmann, B. & Sigworth,

F. J. _Pflügers Arch. ges. Physiol._ 391, 85–100 (1981). Article  CAS  Google Scholar  * Moonen, G., Neale, E. A., Macdonald, R. L., Warren, G. & Nelson, P. G. _Devl Brain Res._ 5, 59–73

(1982). Article  Google Scholar  * Weber, A. & Schachner, M. _Brain Res._ 311, 119–130 (1984). Article  CAS  PubMed  Google Scholar  * Gruol, D. L. _Brain Res._ 263, 223–241 (1983).

Article  CAS  PubMed  Google Scholar  * Cull-Candy, S. G. & Usowicz, M. M. _Brain Res._ (in the press). * Crepel, F., Dupont, J.-L. & Gardette, R. _Brain Res._ 279, 311–315 (1983).

Article  CAS  PubMed  Google Scholar  * Nowak, L., Bregestovski, P., Ascher, P., Herbet, A. & Prochiantz, A. _Nature_ 307, 462–465 (1984). Article  ADS  CAS  PubMed  Google Scholar  *

Cull-Candy, S. G. & Ogden, D. C. _Proc. R. Soc._ B224, 367–373 (1985). ADS  Google Scholar  * Katz, B. & Miledi, R. _J. Physiol., Lond._ 224, 665–699 (1972). Article  CAS  PubMed 

PubMed Central  Google Scholar  * Anderson, C. R. & Stevens, C. F. _J. Physiol., Lond._ 235, 655–691 (1973). Article  CAS  PubMed  PubMed Central  Google Scholar  * Ascher, P., Nowak, L.

& Kehoe, J. S. in _Ion Channels in Neural Membranes_ (eds Ritchie, J. M., Keynes, R. D. & Bolis, L.) 823–295 (Liss, New York, 1986). Google Scholar  * Ishida, A. T. & Neyton, J.

_Proc. natn. Acad. Sci. U.S.A._ 82, 1837–1841 (1985). Article  ADS  CAS  Google Scholar  * Hamill, O. P. & Sakmann, B. _Nature_ 294, 462–464 (1981). Article  ADS  CAS  PubMed  Google

Scholar  * Trautmann, A. _Nature_ 298, 272–275 (1982). Article  ADS  CAS  PubMed  Google Scholar  * Läuger, P. _Biophys. J._ 47, 581–590 (1985). Article  ADS  PubMed  PubMed Central  Google

Scholar  * MacDermott, A. B., Mayer, M. L., Westbrook, G. L., Smith, S. J. & Barker, J. L. _Nature_ 321, 519–522 (1986). Article  ADS  CAS  PubMed  Google Scholar  * Ascher, P. &

Nowak, L. _J. Physiol., Lond._ 377, 35P (1986). Google Scholar  * Mayer, M. L., Westbrook, G. L. & Guthrie, P. B. _Nature_ 309, 261–263 (1984). Article  ADS  CAS  PubMed  Google Scholar

  * Colquhoun, D. & Sigworth, F. J. in _Single Channel Recording_ (eds Sakmann, B. & Neher, E.) 191–264 (Plenum, New York, 1983). Book  Google Scholar  * Cull-Candy, S. G. &

Ogden, D. C. in _Ion Channels in Neural Membranes_ (eds Ritchie, J. M., Keynes, R. D. & Bolis, L.) 297–308 (Liss, New York, 1986). Google Scholar  Download references AUTHOR INFORMATION

AUTHORS AND AFFILIATIONS * MRC Receptor Mechanisms Research Group, Department of Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK Stuart G. Cull-Candy & Maria

M. Usowicz Authors * Stuart G. Cull-Candy View author publications You can also search for this author inPubMed Google Scholar * Maria M. Usowicz View author publications You can also search

for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Cull-Candy, S., Usowicz, M. Multiple-conductance channels

activated by excitatory amino acids in cerebellar neurons. _Nature_ 325, 525–528 (1987). https://doi.org/10.1038/325525a0 Download citation * Received: 12 September 1986 * Accepted: 27

November 1986 * Issue Date: 05 February 1987 * DOI: https://doi.org/10.1038/325525a0 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get

shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative