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Changes in extracellular K+ evoked by GABA, THIP and baclofen in the guinea-pig hippocampal slice

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Summary

Changes in [K+]0 evoked by the inhibitory amino acid transmitter, GABA (γ-aminobutyric acid) and its agonists were recorded with ion-selective microelectrodes in the CA1 stratum pyramidale of guinea-pig hippocampal slices. Bath applications of GABA (0.1–10 mM) produced dose-dependent increases in [K+]0 (EC50 = 4 mM, Rmax= 1.6 mM), with a peak and decline during exposure, followed by undershoot during recovery. In contrast the selective GABAa agonist, THIP (4,5,6,7-tetrahydroisoxazolo-(5,4-c)-pyridin-3-ol) (0.01–1 mM) showed ≈ ten-fold greater potency and evoked only increases in [K+]0 (EC50 = 0.5 mM, Rmax= 2 mM). Reduction of temperature from 34° to 22° C caused a more than two-fold augmentation of the K0 accumulation evoked by GABA, but no change in that due to THIP. The GABAA antagonist, BMI (bicuculline methiodide) (100 μM) completely blocked responses to THIP and partially antagonized those to GABA. Responses to GABA were synergistically enhanced by pentobarbital (100 μM). Only small, delayed and inconsistent changes could be evoked by relatively high concentrations of the GABAB agonist, DL-baclofen (0.01–1 mM). The K+ changes evoked by GABA appear to be mediated by the activation of GABAA receptors with low affinity and to be related to their depolarizing action. Although the response includes an electrogenic component which suggests the involvement of Na-dependent transmitter uptake/transport, the increase in k +0 probably reflects an outward counter/co-transport of K+ with Cl/HCO3 anion shifts and/or activation of a voltage-dependent K+ conductance.

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References

  • Aickin CC, Deisz RA, Lux HD (1984) Mechanisms of chloride transport in crayfish stretch receptor neurones and guinea pig vas deferens: implications for inhibition mediated by GABA. Neurosci Lett 47:239–244

    Google Scholar 

  • Alger BE, Nicoll RA (1982) Pharmacological evidence for two kinds of GABA receptor on rat hippocampal pyramidal cells studied in vitro. J Physiol (Lond) 328:125–141

    Google Scholar 

  • Andersen P, Dingledine R, Gjerstad L, Langmoen IA, Mosfeldt Laursen A (1980) Two different responses of hippocampal pyramidal cells to application of gamma-amino butyric acid. J Physiol (Lond) 305:279–296

    Google Scholar 

  • Avoli M, Perreault P (1987) A GABAergic depolarizing potential in the hippocampus disclosed by the convulsant 4-aminopyridine. Brain Res 400:191–195

    Google Scholar 

  • Ballanyi K, Grafe P (1985) An intracellular analysis of gammaaminobutyric acid-associated ion movements in rat sympathetic neurones. J Physiol (Lond) 365:41–58

    Google Scholar 

  • Ballanyi K, Grafe P, Reddy MM, Ten Bruggencate G (1984) Different types of potassium transport linked to carbachol and γ-aminobutyric acid actions in rat sympathetic neurons. Neuroscience 12:917–927

    Google Scholar 

  • Barker JL, Nicoll RA (1973) The pharmacology and ionic dependence of amino acid responses in the frog spinal cord. J Physiol (Lond) 228:259–277

    Google Scholar 

  • Barolet AW, Andrews R, Morris ME (1989) Ion-selective microelectrode calibration: flow-system and calibration software. J Neurosci Meth 30:263–266

    Google Scholar 

  • Barolet AW, Kish SJ, Morris ME (1985) Identification of extrasynaptic binding sites for [3H]GABA in peripheral nerve. Brain Res 358:104–109

    Google Scholar 

  • Barolet AW, Morris ME (1987) Changes in extracellular potassium evoked by GABA agonists in the hippocampal slice. Neuroscience Abstr 13:955

    Google Scholar 

  • Bowery NG, Hudson AL, Price GW (1987) GABAA and GABAB receptor site distribution in the rat central nervous system. Neuroscience 20:365–383

    Google Scholar 

  • Bowery NG, Price GW, Hudson AL, Hill DR, Wilkin GP, Turnbull MJ (1984) GABA receptor multiplicity: visualization of different receptor types in the mammalian CNS. Neuropharmacology 23:219–231

    Google Scholar 

  • Bührle CP, Sonnhof U (1985) The ionic mechanism of postsynaptic inhibition in motoneurones of the frog spinal cord. Neuroscience 14:581–592

    Google Scholar 

  • Coles JA, Tsacopoulos M (1977) A method of making fine double-barrelled potassium-sensitive micro-electrodes for intracellular recording. J Physiol (Lond) 270:12P

    Google Scholar 

  • Czeh G, Obih J-CA, Somjen GG (1987) The effect of changing extracellular potassium concentration on synaptic transmission in isolated spinal cords. Brain Res 446:50–60

    Google Scholar 

  • Deisz RA, Lux D (1982) The role of intracellular chloride in hyperpolarizing post-synaptic inhibition of crayfish stretch receptor neurones. J Physiol (Lond) 326:123–138

    Google Scholar 

  • Deschenes M, Feltz P (1976) GABA-induced rise in extracellular potassium in rat dorsal root ganglia: an electrophysiological study in vivo. Brain Res 118:494–499

    Google Scholar 

  • Dietzel I, Heinemann U, Hofmeier G, Lux HD (1980) Transient changes in the size of the extracellular space in the sensorimotor cortex of cats in relation to stimulus-induced changes in potassium concentration. Exp Brain Res 40:432–439

    Google Scholar 

  • Drew CA, Johnston GAR, Weatherby RP (1984) Bicucilline-insensitive GABA receptors: studies on the binding of (-)baclofen to rat cerebellar membranes. Neurosci Lett 52:317–321

    Google Scholar 

  • Gähwiler BH, Brown DA (1985) GABAB-receptor activated a k+ current in voltage-clamped CA3 pyramidal cells in hippocampal cultures. Proc of Nat Acad Sci USA 82:1558–1562

    Google Scholar 

  • Gallagher JP, Shinnick-Gallagher P (1983) Electrophysiological characteristics of GABA-receptor complexes. In: Enna SJ (ed) The GABA receptors. Humana Press, New Jersey, pp 25–61

    Google Scholar 

  • Guilbault GG, Durst RA, Frant MS, Freiser H, Hansen EH, Light TS, Pungor E, Rechnitz G, Rice NM, Rohm TJ, Simon W, Thomas JDR (1976) Recommendations for nomenclature of ion-selective electrodes. Pure Appl Chem 48:127–145

    Google Scholar 

  • Gutnick MJ, Segal M (1981) Serotonin and GABA-induced fluctuations in extracellular ion concentration in the hippocampal slice. In: Syková E, Hnik P, Vyklicky L (eds) Ion-selective microelectrodes and their use in excitable tissues. Plenum Press, New York, pp 261–266

    Google Scholar 

  • Harris RA, Allan AM (1985) Functional coupling of γ-aminobutyric acid receptors to chloride channels in brain membranes. Science 228:1108–1110

    Google Scholar 

  • Howe JR, Sutor B, Zieglgänsberger W (1987) Baclofen reduces post-synaptic potentials of rat cortical neurones by an action other than its hyperpolarizing action. J Physiol (Lond) 384:539–569

    Google Scholar 

  • Huguenard JR, Alger BE (1986) Whole-cell voltage-clamp study of the fading of GABA-activated currents in acutely dissociated hippocampal neurons. J Neurophysiol 56:1–18

    Google Scholar 

  • Inoue M, Matsuo T, Ogata N (1985a) Characterization of pre- and postsynaptic actions of (-)-baclofen in the guinea-pig hippocampus in vitro. Br J Pharmacol 84:843–851

    Google Scholar 

  • Inoue M, Matsuo T, Ogata N (1985b) Possible involvement of K+-conductance in the action of γ-aminobutyric acid in the guinea-pig hippocampus. Br J Pharmacol 86:515–524

    Google Scholar 

  • Kaila K, Pasternack M, Saarikoski J, Voipio J (1989) Influence of GABA-gated bicarbonate conductance on potential, current and intracellular chloride in crayfish muscle fibres. J Physiol (Lond) 416:161–181

    Google Scholar 

  • Kanner BI, Radian R (1984) Ion-coupled neurotransmitter transport across the synaptic plasma membrane. Ann New York Acad Sci 198:153–161

    Google Scholar 

  • Kocsis JD, Malenka RC, Waxman SG (1983) Effects of extracellular potassium concentration on the excitability of the parallel fibres of the rat cerebellum. J Physiol (Lond) 334:225–244

    Google Scholar 

  • Korn SJ, Dingledine R (1986) Inhibition of GABA uptake in the rat hippocampal slice. Brain Res 368:247–255

    Google Scholar 

  • Krnjević K (1981) Desensitization of GABA receptors. In: Costa E et al (eds) GABA and benzodiazepine receptors. Raven Press, New York, pp 111–120

    Google Scholar 

  • Krnjević K, Morris ME (1972) Extracellular K+ activity and slow potential changes in spinal cord and medulla. Can J Physiol Pharmacol 50:1214–1217

    Google Scholar 

  • Krogsgaard-Larsen P, Falch E, Schousboe A, Curtis DR (1986) GABA agonists and uptake inhibitors: stereoselectivities and anticonvulsant effects. In: Nisticò G et al (eds) Neurotransmitters, seizures, and epilepsy, III. Raven Press, New York, pp 135–150

    Google Scholar 

  • Krogsgaard-Larsen P, Falch E, Schousboe A, Curtis DR, Johston GAR (1980) Piperidine-4-sulphonic acid, a new specific GABA agonist. J Neurochem 34:756–759

    Google Scholar 

  • Kudo Y, Fukuda H (1976) Alteration of extracellular K+-activity induced by amino acids in the frog spinal cord. Jpn J Pharmacol 26:385–387

    Google Scholar 

  • Loeffler JP, Desaulles E, Demeneix BA, Feltz P (1982) Electrophysiological study with K+-and Ca2+-sensitive micropipettes of GABA receptors in the rat neurointermediate lobe in vitro. Neurosci Lett 34:271–276

    Google Scholar 

  • Morris ME, Di Costanzo GA, Barolet A, Sheridan PJ (1983) Role of K+ in GABA (gamma-aminobutyric acid)-evoked depolarization of peripheral nerve. Brain Res 278:127–135

    Google Scholar 

  • Morris ME, Krnjević K (1974) Some measurements of extracellular potassium activity in the mammalian central nervous system. In: Berman HJ, Hebert NC (eds) Proceedings of workshop on ion-selective microelectrodes. Advances Expl Med Biol 50:129–143

  • Morris ME, Krnjević K, MacDonald JF (1985) Changes in intracellular free Ca ion concentration, evoked by electrical activity in rat spinal neurons in situ. Neuroscience 14:536–580

    Google Scholar 

  • Mueller AL, Taube JS, Schwartzkroin PA (1984) Development of hyperpolarizing inhibitory postsynaptic potentials and hyperpolarizing response to γ-aminobutyric acid in rabbit hippocampus studied in vitro. J Neurosci 4:860–867

    Google Scholar 

  • Müller W, Misgeld U, Lux HD (1989) γ-Aminobutyric acid-induced ion movements in the guinea pig hippocampal slice. Brain Res 484:184–191

    Google Scholar 

  • Newberry NR, Nicoll RA (1984) A bicuculline-resistant inhibitory post-synaptic potential in rat hippocampal pyramidal cells in vitro. J Physiol (Lond) 348:239–254

    Google Scholar 

  • Newberry NR, Nicoll RA (1985) Comparison of the action of baclofen with γ-aminobutyric acid on rat hippocampal pyramidal cells in vitro. J Physiol (Lond) 360:161–185

    Google Scholar 

  • Oehme M, Simon W (1976) Microelectrode for potassium ions based on a neutral carrier and comparison of its characteristics with a cation exchanger sensor. Anal Chim Acta 86:21–24

    Google Scholar 

  • Segal M, Gutnick MJ (1980) Effects of serotonin on extracellular potassium concentration in the rat hippocampal slice. Brain Res 195:389–401

    Google Scholar 

  • Syková E (1979) GABA-induced changes of extra-cellular K+-activity in the frog spinal cord. Physiol Bohemoslov 28:189–192

    Google Scholar 

  • Syková E (1983) Extracellular K+ accumulation in the central nervous system. Prog Biophys Molec Biol 42:135–189

    Google Scholar 

  • Ubert U, Krnjević K (1990) Systemic CI-966, a new GABA uptake blocker, enhances GABA-action in CA1 pyramidal layer in situ. Can J Physiol Pharmacol 68:1194–1199

    Google Scholar 

  • Wong RKS, Watkins DJ (1982) Cellular factors influencing GABA responses in hippocampal pyramidal cells. J Neurophysiol 48:938–951

    Google Scholar 

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Authors and Affiliations

  1. Department of Pharmacology, University of Toronto, M5S 1A8, Toronto, Ont., Canada

    A. W. Barolet & M. E. Morris

  2. Departments of Medicine and Pharmacology, University of Ottawa, 451 Smyth Road, K1H 8M5, Ottawa, Ont., Canada

    A. W. Barolet & M. E. Morris

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  1. A. W. Barolet
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  2. M. E. Morris
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Barolet, A.W., Morris, M.E. Changes in extracellular K+ evoked by GABA, THIP and baclofen in the guinea-pig hippocampal slice. Exp Brain Res 84, 591–598 (1991). https://doi.org/10.1007/BF00230971

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  • DOI: https://doi.org/10.1007/BF00230971

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