Summary
The action of inhibitory amino acid transmitters GABA, glycine, β-alanine and taurine has been studied on the membrane potential of cultured astrocytes and on the extracellular K+-concentration ([K+]0) using K+-sensitive microelectrodes. All four amino acids caused a depolarization of glial cells and an increase of [K+]0. The effects produced by GABA were usually more pronounced than those caused by the other amino acids. Simultaneous recordings of the action of GABA and glycine on the glial membrane potential and on [K+]0 usually revealed a good correlation in time course, but often there were differences between the amplitudes of glial depolarizations and the values calculated from the [K+]0 increase. 4-Aminopyridine, which blocks K+-conductance of excitable membranes, reversibly abolished both the glial depolarization and the [K+]0 increase produced by GABA and glycine. From these results it is concluded that unlike neurones, glial cells do not have receptors for these amino acid transmitters and that their action on glial cells is caused by the efflux of K+ from activated neurones.
Similar content being viewed by others
References
Barker JL, Ransom BR (1978) Amino acid pharmacology of mammalian central neurones grown in tissue culture. J Physiol (Lond) 280: 331–354
Berridge MJ, Schlue WR (1978) Ion-selective electrode studies on the effects of 5-hydroxytryptamine on the intracellular level of potassium in an insect salivary gland. J Exp Biol 72: 203–216
Bruggencate ten G, Lux HD, Liebl L (1974) Possible relationship between extracellular potassium activity and presynaptic inhibition in the spinal cord of the cat. Pflügers Arch 349: 301–317
Cordingley GE, Somjen GG (1978) The clearing of excess potassium from extracellular space in spinal cord and cerebral cortex. Brain Res 151: 291–306
Curtis DR, Hösli L, Johnston GAR, Johnston IH (1968) The hyperpolarization of spinal motoneurones by glycine and related amino acids. Exp Brain Res 5: 235–258
DeFeudis FV, Ossola L, Schmitt G, Wolff P, Mandel P (1980) Na+-independent binding of (3H)GABA and (3H)muscimol to subcellular particles of neural primary cultures and whole brain. J Neurochem 34: 216–218
Deschenes M, Feltz P (1976) GABA-induced rise of extracellular potassium in rat dorsal root ganglia: an electrophysiological study in vivo. Brain Res 118: 494–499
Eccles JC (1957) The physiology of nerve cells. Johns Hopkins Press, Baltimore, p 270
Grossman RG, Whiteside L, Hampton TL (1969) The time course of evoked depolarization of cortical glial cells. Brain Res 14: 401–415
Hertz L (1965) Possible role of neuroglia: A potassium-mediated neuronal-neuroglial-neuronal impulse transmission system. Nature 206: 1091–1094
Hösli L, Hösli E (1978) Action and uptake of neurotransmitters in CNS tissue culture. Rev Physiol Biochem Pharmacol 81: 135–188
Hösli E, Hösli L (1980a) Autoradiographic localization of 3H-GABA and 3H-muscimol binding in rat cerebellar cultures. Exp Brain Res 38: 241–243
Hösli E, Hösli L (1980b) Cellular localization of the uptake of (3H)taurine and (3H)β-alanine in cultures of the rat central nervous system. Neuroscience 5: 145–152
Hösli L, Hösli E, Andres PF (1973) Nervous tissue culture — a model to study action and uptake of putative neurotransmitters such as amino acids. Brain Res 62: 597–602
Hösli L, Hösli E, Andrès PF, Wolff JR (1975) Amino acid transmitters — action and uptake in neurons and glial cells of human and rat CNS tissue culture. In: Santini M (ed) Golgi centennial symposium. Proceedings. Raven Press, New York, pp 473–488
Hösli L, Andrès PF, Hösli E (1978) Neuron-glia interactions: Indirect effect of GABA on cultured glial cells. Exp Brain Res 33: 425–434
Hösli L, Andrès PF, Hösli E (1979a) Effects of 4-aminopyridine and tetraethylammonium on the depolarization by GABA of cultured satellite glial cells. Neurosci Lett 11: 193–196
Hösli L, Andrès PF, Hösli E (1979b) Depolarization of cultured astrocytes by glutamate and aspartate. Neuroscience 4: 1593–1598
Hösli L, Andrès PF, Hösli E (1979c) Action of amino acid transmitters on cultured glial cells of the mammalian peripheral and central nervous system. J Physiol (Paris) 75: 655–659
Hösli E, Möhler H, Richards JG, Hösli L (1980a) Autoradiographic localization of binding sites for 3H-GABA, 3H-muscimol, (+)3H-bicuculline-methiodide and 3H-flunitrazepam in cultures of rat cerebellum and spinal cord. Neuroscience 5: 1657–1665
Hösli L, Andrès PF, Hösli E (1980b) Neurone-glia interaction: effects of GABA on glial cells in tissue culture. Brain Res Bull [Suppl 2] 5: 6
Hösli L, Hösli E, Andres PF, Landolt H (1980c) GABA and glycine receptors in CNS cultures: Autoradiographic binding and electrophysiological studies. In: Mandel P, DeFeudis FV (eds) Proceedings of the symposium “Amino acid transmitters”. Raven Press, New York (in press)
Kim SU, Oh TH, Johnson DD (1972) Developmental changes of acetylcholinesterase and pseudocholinesterase in organotypic cultures of spinal cord. Exp Neurol 35: 274–281
Krnjević K (1974) Chemical nature of synaptic transmission in vertebrates. Physiol Rev 54: 418–540
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
Kuffler SW, Nicholls JG (1966) The physiology of neuroglia cells. Rev Physiol Biochem Pharmacol 62: 1–90
Lux HD, Neher E (1973) The equilibration time course of [K+]0 in cat cortex. Exp Brain Res 17: 190–205
Meves H, Pichon Y (1977) The effect of internal and external 4-aminopyridine on the potassium currents in intracellularly perfused squid giant axons. J Physiol (Lond) 268: 511–532
Neher E, Lux HD (1973) Rapid changes of potassium concentration at the outer surface of exposed single neurons during membrane current flow. J Gen Physiol 61: 385–399
Ossola L, DeFeudis FV, Mandel P (1980) Lack of Na+-independent binding of (3H)GABA or (3H)muscimol to particulate fractions of cultured astroblasts. J Neurochem 34: 1026–1029
Ransom BR, Goldring S (1973) Ionic determinants of membrane potential of cells presumed to be glia in cerebral cortex of cat. J Neurophysiol 36: 855–868
Ransom BR, Nelson PG (1975) Neuropharmacological responses from nerve cells in tissue culture. In: Iversen LL, Iversen SD, Snyder SH (eds) Psychopharmacology, vol 2. Plenum Press, New York, pp 101–127
Schlue WR, Deitmer JW (1980) Extracellular potassium in neuropile and nerve cell body region of the leech central nervous system. J Exp Biol 87: 23–43
Schlue WR, Walz W (1979) Physiological properties of neuropile glial cells in the central nervous system of the leech. Pflügers Arch [Suppl] 379: R39
Schousboe A, Svenneby G, Hertz L (1977) Uptake and metabolism of glutamate in astrocytes cultured from dissociated mouse brain hemispheres. J Neurochem 29: 999–1005
Schrier BK, Thompson EJ (1974) On the role of glial cells in the mammalian nervous system. Uptake, excretion, and metabolism of putative neurotransmitters by cultured glial tumor cells. J Biol Chem 249: 1769–1780
Sellström Å, Hamberger A (1976) γ-Aminobutyric acid release from neurons and glia. Acta Physiol Scand 98: 94–102
Somjen GG (1975) Electrophysiology of neuroglia. Ann Rev Physiol 37: 163–190
Sonnhof U, Grafe P, Richter DW, Parekh N, Krumnikl G, Linder M (1978) Investigations of the effects of glutamate on motoneurons of the isolated frog spinal cord. In: Ryall RW, Kelly JS (eds) Iontophoresis and transmitter mechanisms in the mammalian central nervous system. Elsevier/North-Holland Biomedical Press, Amsterdam, pp 391–393
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Hösli, L., Hösli, E., Andrès, P.F. et al. Evidence that the depolarization of glial cells by inhibitory amino acids is caused by an efflux of K+ from neurones. Exp Brain Res 42, 43–48 (1981). https://doi.org/10.1007/BF00235727
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00235727