Abstract
1. Outside-out patches were isolated from granule cells of dentate gyrus and pyramidal cells of CA3 and CA1 regions of rat hippocampal slices. Patches were exposed briefly to L-glutamate using a piezo-driven double-barrelled application pipette. 2. Applications of glutamate (1 mM) of 1 ms duration activated patch currents which rose and decayed rapidly. The 20-80% rise time of these glutamate receptor (GluR)-mediated currents was usually 0.2-0.6 ms. At -50 mV the peak current varied from 10 to 500 pA in different patches. 3. The peak current-voltage relation for brief pulses of 1 mM glutamate was virtually linear in normal extracellular solution for patches from the three cell types (-100 to 60 mV). 4. The permeability of GluR channels activated at the peak to Ca2+, relative to K+, was less than 0.1 for all three cell types (under bi-ionic conditions with Ca2+ on the extracellular side and K+ on the intracellular side of the membrane). 5. The offset decay time constant of the current following 1 ms pulses of 1 mM glutamate was brief, with mean values of 3.0 +/- 0.8, 2.5 +/- 0.7, and 2.3 +/- 0.7 ms for dentate, CA3 and CA1 cell patches, respectively. Offset time constants were independent of membrane potential and independent of glutamate concentration (200 microM and 1 mM) for the three cell types. 6. Applications of 1 mM glutamate of 100 ms duration showed that glutamate responses desensitized rapidly. The time constants for desensitization were 9.4 +/- 2.7, 11.3 +/- 2.8, and 9.3 +/- 2.8 ms for patches from dentate, CA3 and CA1 cells respectively. Desensitization time constants were only weakly dependent on glutamate concentration (200 microM and 1 mM) for the three cell types. Thus offset time constants are about four times faster than desensitization time constants for both glutamate concentrations. 7. Double pulse application of glutamate indicated that even a 1 ms pulse of 1 mM glutamate causes partial (about 60%) desensitization of GluR channels. The time course of recovery from desensitization was slower in dentate gyrus granule cell patches than in CA3 or CA1 pyramidal cell patches. 8. Desensitization was studied at equilibrium by exposing patches to low glutamate concentrations for at least 15 s before a 1 ms test pulse of 1 mM glutamate.(ABSTRACT TRUNCATED AT 400 WORDS)
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- Alger B. E., Teyler T. J. Long-term and short-term plasticity in the CA1, CA3, and dentate regions of the rat hippocampal slice. Brain Res. 1976 Jul 16;110(3):463–480. doi: 10.1016/0006-8993(76)90858-1. [DOI] [PubMed] [Google Scholar]
- Anderson C. R., Stevens C. F. Voltage clamp analysis of acetylcholine produced end-plate current fluctuations at frog neuromuscular junction. J Physiol. 1973 Dec;235(3):655–691. doi: 10.1113/jphysiol.1973.sp010410. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Benveniste H., Drejer J., Schousboe A., Diemer N. H. Elevation of the extracellular concentrations of glutamate and aspartate in rat hippocampus during transient cerebral ischemia monitored by intracerebral microdialysis. J Neurochem. 1984 Nov;43(5):1369–1374. doi: 10.1111/j.1471-4159.1984.tb05396.x. [DOI] [PubMed] [Google Scholar]
- Bettler B., Boulter J., Hermans-Borgmeyer I., O'Shea-Greenfield A., Deneris E. S., Moll C., Borgmeyer U., Hollmann M., Heinemann S. Cloning of a novel glutamate receptor subunit, GluR5: expression in the nervous system during development. Neuron. 1990 Nov;5(5):583–595. doi: 10.1016/0896-6273(90)90213-y. [DOI] [PubMed] [Google Scholar]
- Blake J. F., Yates R. G., Brown M. W., Collingridge G. L. 6-Cyano-7-nitroquinoxaline-2,3-dione as an excitatory amino acid antagonist in area CA1 of rat hippocampus. Br J Pharmacol. 1989 May;97(1):71–76. doi: 10.1111/j.1476-5381.1989.tb11925.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Boulter J., Hollmann M., O'Shea-Greenfield A., Hartley M., Deneris E., Maron C., Heinemann S. Molecular cloning and functional expression of glutamate receptor subunit genes. Science. 1990 Aug 31;249(4972):1033–1037. doi: 10.1126/science.2168579. [DOI] [PubMed] [Google Scholar]
- Burnashev N., Monyer H., Seeburg P. H., Sakmann B. Divalent ion permeability of AMPA receptor channels is dominated by the edited form of a single subunit. Neuron. 1992 Jan;8(1):189–198. doi: 10.1016/0896-6273(92)90120-3. [DOI] [PubMed] [Google Scholar]
- Colquhoun D., Hawkes A. G. A note on correlations in single ion channel records. Proc R Soc Lond B Biol Sci. 1987 Feb 23;230(1258):15–52. doi: 10.1098/rspb.1987.0008. [DOI] [PubMed] [Google Scholar]
- Colquhoun D., Hawkes A. G. Relaxation and fluctuations of membrane currents that flow through drug-operated channels. Proc R Soc Lond B Biol Sci. 1977 Nov 14;199(1135):231–262. doi: 10.1098/rspb.1977.0137. [DOI] [PubMed] [Google Scholar]
- Colquhoun D., Sakmann B. Fast events in single-channel currents activated by acetylcholine and its analogues at the frog muscle end-plate. J Physiol. 1985 Dec;369:501–557. doi: 10.1113/jphysiol.1985.sp015912. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cull-Candy S. G., Usowicz M. M. Multiple-conductance channels activated by excitatory amino acids in cerebellar neurons. Nature. 1987 Feb 5;325(6104):525–528. doi: 10.1038/325525a0. [DOI] [PubMed] [Google Scholar]
- Dingledine R., Boland L. M., Chamberlin N. L., Kawasaki K., Kleckner N. W., Traynelis S. F., Verdoorn T. A. Amino acid receptors and uptake systems in the mammalian central nervous system. Crit Rev Neurobiol. 1988;4(1):1–96. [PubMed] [Google Scholar]
- Dodt H. U., Zieglgänsberger W. Visualizing unstained neurons in living brain slices by infrared DIC-videomicroscopy. Brain Res. 1990 Dec 24;537(1-2):333–336. doi: 10.1016/0006-8993(90)90380-t. [DOI] [PubMed] [Google Scholar]
- Dudel J., Franke C., Hatt H., Ramsey R. L., Usherwood P. N. Glutamatergic channels in locust muscle show a wide time range of desensitization and resensitization characteristics. Neurosci Lett. 1990 Jul 3;114(2):207–212. doi: 10.1016/0304-3940(90)90073-i. [DOI] [PubMed] [Google Scholar]
- Dudel J., Franke C., Hatt H., Ramsey R. L., Usherwood P. N. Rapid activation and desensitization by glutamate of excitatory, cation-selective channels in locust muscle. Neurosci Lett. 1988 May 16;88(1):33–38. doi: 10.1016/0304-3940(88)90311-4. [DOI] [PubMed] [Google Scholar]
- Dudel J., Franke C., Hatt H. Rapid activation, desensitization, and resensitization of synaptic channels of crayfish muscle after glutamate pulses. Biophys J. 1990 Mar;57(3):533–545. doi: 10.1016/S0006-3495(90)82569-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Edwards F. A., Konnerth A., Sakmann B., Takahashi T. A thin slice preparation for patch clamp recordings from neurones of the mammalian central nervous system. Pflugers Arch. 1989 Sep;414(5):600–612. doi: 10.1007/BF00580998. [DOI] [PubMed] [Google Scholar]
- Egebjerg J., Bettler B., Hermans-Borgmeyer I., Heinemann S. Cloning of a cDNA for a glutamate receptor subunit activated by kainate but not AMPA. Nature. 1991 Jun 27;351(6329):745–748. doi: 10.1038/351745a0. [DOI] [PubMed] [Google Scholar]
- Franke C., Hatt H., Dudel J. Liquid filament switch for ultra-fast exchanges of solutions at excised patches of synaptic membrane of crayfish muscle. Neurosci Lett. 1987 Jun 15;77(2):199–204. doi: 10.1016/0304-3940(87)90586-6. [DOI] [PubMed] [Google Scholar]
- Gibb A. J., Colquhoun D. Activation of N-methyl-D-aspartate receptors by L-glutamate in cells dissociated from adult rat hippocampus. J Physiol. 1992 Oct;456:143–179. doi: 10.1113/jphysiol.1992.sp019331. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hamill O. P., Marty A., Neher E., Sakmann B., Sigworth F. J. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 1981 Aug;391(2):85–100. doi: 10.1007/BF00656997. [DOI] [PubMed] [Google Scholar]
- Hestrin S., Nicoll R. A., Perkel D. J., Sah P. Analysis of excitatory synaptic action in pyramidal cells using whole-cell recording from rat hippocampal slices. J Physiol. 1990 Mar;422:203–225. doi: 10.1113/jphysiol.1990.sp017980. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hollmann M., Hartley M., Heinemann S. Ca2+ permeability of KA-AMPA--gated glutamate receptor channels depends on subunit composition. Science. 1991 May 10;252(5007):851–853. doi: 10.1126/science.1709304. [DOI] [PubMed] [Google Scholar]
- Hollmann M., O'Shea-Greenfield A., Rogers S. W., Heinemann S. Cloning by functional expression of a member of the glutamate receptor family. Nature. 1989 Dec 7;342(6250):643–648. doi: 10.1038/342643a0. [DOI] [PubMed] [Google Scholar]
- Inoue M., Kuriyama H. Properties of the nicotinic-receptor-activated current in adrenal chromaffin cells of the guinea-pig. Pflugers Arch. 1991 Aug;419(1):13–20. doi: 10.1007/BF00373741. [DOI] [PubMed] [Google Scholar]
- Johnston D., Brown T. H. Interpretation of voltage-clamp measurements in hippocampal neurons. J Neurophysiol. 1983 Aug;50(2):464–486. doi: 10.1152/jn.1983.50.2.464. [DOI] [PubMed] [Google Scholar]
- Jonas P., Sakmann B. Glutamate receptor channels in isolated patches from CA1 and CA3 pyramidal cells of rat hippocampal slices. J Physiol. 1992 Sep;455:143–171. doi: 10.1113/jphysiol.1992.sp019294. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Katz B., Miledi R. The nature of the prolonged endplate depolarization in anti-esterase treated muscle. Proc R Soc Lond B Biol Sci. 1975 Dec 31;192(1106):27–38. doi: 10.1098/rspb.1975.0149. [DOI] [PubMed] [Google Scholar]
- Keinänen K., Wisden W., Sommer B., Werner P., Herb A., Verdoorn T. A., Sakmann B., Seeburg P. H. A family of AMPA-selective glutamate receptors. Science. 1990 Aug 3;249(4968):556–560. doi: 10.1126/science.2166337. [DOI] [PubMed] [Google Scholar]
- Keller B. U., Konnerth A., Yaari Y. Patch clamp analysis of excitatory synaptic currents in granule cells of rat hippocampus. J Physiol. 1991 Apr;435:275–293. doi: 10.1113/jphysiol.1991.sp018510. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kiskin N. I., Krishtal O. A., Tsyndrenko AYa Excitatory amino acid receptors in hippocampal neurons: kainate fails to desensitize them. Neurosci Lett. 1986 Jan 30;63(3):225–230. doi: 10.1016/0304-3940(86)90360-5. [DOI] [PubMed] [Google Scholar]
- Lerma J., Herranz A. S., Herreras O., Abraira V., Martín del Río R. In vivo determination of extracellular concentration of amino acids in the rat hippocampus. A method based on brain dialysis and computerized analysis. Brain Res. 1986 Oct 1;384(1):145–155. doi: 10.1016/0006-8993(86)91230-8. [DOI] [PubMed] [Google Scholar]
- Lewis C. A. Ion-concentration dependence of the reversal potential and the single channel conductance of ion channels at the frog neuromuscular junction. J Physiol. 1979 Jan;286:417–445. doi: 10.1113/jphysiol.1979.sp012629. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nakanishi N., Shneider N. A., Axel R. A family of glutamate receptor genes: evidence for the formation of heteromultimeric receptors with distinct channel properties. Neuron. 1990 Nov;5(5):569–581. doi: 10.1016/0896-6273(90)90212-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nicholls D., Attwell D. The release and uptake of excitatory amino acids. Trends Pharmacol Sci. 1990 Nov;11(11):462–468. doi: 10.1016/0165-6147(90)90129-v. [DOI] [PubMed] [Google Scholar]
- Nicoll R. A., Malenka R. C., Kauer J. A. Functional comparison of neurotransmitter receptor subtypes in mammalian central nervous system. Physiol Rev. 1990 Apr;70(2):513–565. doi: 10.1152/physrev.1990.70.2.513. [DOI] [PubMed] [Google Scholar]
- Pennefather P., Quastel D. M. Relation between subsynaptic receptor blockade and response to quantal transmitter at the mouse neuromuscular junction. J Gen Physiol. 1981 Sep;78(3):313–344. doi: 10.1085/jgp.78.3.313. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sah P., Hestrin S., Nicoll R. A. Tonic activation of NMDA receptors by ambient glutamate enhances excitability of neurons. Science. 1989 Nov 10;246(4931):815–818. doi: 10.1126/science.2573153. [DOI] [PubMed] [Google Scholar]
- Sather W., Dieudonné S., MacDonald J. F., Ascher P. Activation and desensitization of N-methyl-D-aspartate receptors in nucleated outside-out patches from mouse neurones. J Physiol. 1992 May;450:643–672. doi: 10.1113/jphysiol.1992.sp019148. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Silver R. A., Traynelis S. F., Cull-Candy S. G. Rapid-time-course miniature and evoked excitatory currents at cerebellar synapses in situ. Nature. 1992 Jan 9;355(6356):163–166. doi: 10.1038/355163a0. [DOI] [PubMed] [Google Scholar]
- Sommer B., Keinänen K., Verdoorn T. A., Wisden W., Burnashev N., Herb A., Köhler M., Takagi T., Sakmann B., Seeburg P. H. Flip and flop: a cell-specific functional switch in glutamate-operated channels of the CNS. Science. 1990 Sep 28;249(4976):1580–1585. doi: 10.1126/science.1699275. [DOI] [PubMed] [Google Scholar]
- Stern P., Edwards F. A., Sakmann B. Fast and slow components of unitary EPSCs on stellate cells elicited by focal stimulation in slices of rat visual cortex. J Physiol. 1992 Apr;449:247–278. doi: 10.1113/jphysiol.1992.sp019085. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Trussell L. O., Fischbach G. D. Glutamate receptor desensitization and its role in synaptic transmission. Neuron. 1989 Aug;3(2):209–218. doi: 10.1016/0896-6273(89)90034-2. [DOI] [PubMed] [Google Scholar]
- Verdoorn T. A., Kleckner N. W., Dingledine R. N-methyl-D-aspartate/glycine and quisqualate/kainate receptors expressed in Xenopus oocytes: antagonist pharmacology. Mol Pharmacol. 1989 Mar;35(3):360–368. [PubMed] [Google Scholar]
- Yamada K. A., Dubinsky J. M., Rothman S. M. Quantitative physiological characterization of a quinoxalinedione non-NMDA receptor antagonist. J Neurosci. 1989 Sep;9(9):3230–3236. doi: 10.1523/JNEUROSCI.09-09-03230.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]