Skip to main content
SpringerLink
Log in

An Electrogenic Ionic Pump Derived from an Ionotropic Receptor: Assessment of a Candidate

  • Commentary
  • Published:
Cellular and Molecular Neurobiology Aims and scope Submit manuscript

Abstract

1.Data obtained studying permeability characteristics of single Deiters' membranes in a microchamber system show that intracellular GABA can activate chloride in → out passage with a GABAA pharmacology.

2.The overall data suggest the presence of a chloride extrusion pump in these neurons based on intracellular GABA activated chloride channels.

3.This conclusion takes up a previous theoretical suggestion that ionic channels could work as ionic pumps provided an energy input modifies the energy profile along the permeation path.

4.According to our quantitative evaluation, this pumping mechanism works with a low yield and along a cycle with a strongly asymmetric behavior, being far from equilibrium due to powerful “leakage” pathways for chloride in these neurons.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

REFERENCES

  • Akaike, T., Fanardjian, V. V., Ito, M., Kumada, M., and Nakajima, H. (1973a). Electrophysiological analysis of the vestibulospinal reflex pathway of rabbit. I. Classification of tract cells. Exp. Brain Res. 17:477–496.

    Google Scholar 

  • Akaike, T., Fanardjian, V. V., Ito, M., and Ohno, T. (1973b). Electrophysiological analysis of the vestibulospinal reflex pathway of rabbit. II. Synaptic actions upon spinal neurones. Exp. Brain Res. 17:497–515.

    Google Scholar 

  • Alberts, B., Bray, D., Lewis, L., Raff, M., and Watson, J. D. (eds.) (1994). Molecular Biology of the Cell, Garland, New York and London, Chap. 12.

  • Ames, G. F. L., and Lecar, H. (1992). ATP-dependent bacterial transporters and cystic fibrosis: analogy between channels and transporters. FASEB J. 6:2660–2666.

    Google Scholar 

  • Backus, K. H., Arigoni, M., Drescher, U., Scheurer, L., Malherbe, P., Mohler, H., and Benson, J. A. (1993). Stoichiometry of a recombinant GABAA receptor deduced from mutation induced rectification. Neuroreport 5:285–288.

    Google Scholar 

  • Cammack, J. N., and Schwartz, E. A. (1996). Channel behavior in a γ-aminobutyrate transporter. Proc. Natl. Acad. Sci. USA 93:723–727.

    Google Scholar 

  • Cammack, J. N., Rakhilin, S. V., and Schwartz, E. A. (1994). A GABA transporter operates asymmetrically and with variable stoichiometry. Neuron 13:949–960.

    Google Scholar 

  • Chang, Y., Wang, R., Barot, S., and Weiss, D. S. (1996). Stoichiometry of a recombinant GABAA receptor. J. Neurosci. 16:5415–5424.

    Google Scholar 

  • Cupello, A., Palm, A., Rapallino, M. V., and Hydén, H. (1991). Can Cl− ions be extruded from a γ-aminobutyric acid (GABA)-acceptive nerve cell via GABAA receptors on the plasma membrane cytoplasmic side? Cell. Mol. Neurobiol. 11:333–346.

    Google Scholar 

  • Dani, J. A. (1986). Ion-channel entrances influence permeation: Net charge, size, shape and binding considerations. Biophys. J. 49:607–618.

    Google Scholar 

  • De Felice, L. J., and Blakely, R. D. (1996). Pore models for transporters? Biophys. J. 70:579–580.

    Google Scholar 

  • Fairman, W. A., Vanderberg, R. J., Arriza, J. L., Kavanaugh, M. P., and Amara, S. G. (1995). An excitatory amino-acid transporter with properties of a ligand-gated chloride channel. Nature 375:599–603.

    Google Scholar 

  • Gadsby, D. C., Rakowski, R. F., and De Weer, P. (1993). Extracellular access to the Na,K pump: Pathway similar to ion channel. Science 260:100–103.

    Google Scholar 

  • Grillner, S., Hongo, T., and Lund, S. (1970). The vestibulospinal tract. Effect on alpha-motoneurones in lumbosacral spinal cord in the cat. Exp. Brain Res. 10:94–120.

    Google Scholar 

  • Higgins, C. F. (1995). The ABC of channel regulation. Cell 82:693–696.

    Google Scholar 

  • Hilgeman, D. W. (1994). Channel-like function of the Na,K pump probed at microsecond resolution in giant membrane patches. Science 263:1429–1432.

    Google Scholar 

  • Hille, B. (ed.) (1992). Ion Channels of Excitable Membranes, Sinauer, Sunderland, MA, Chap. 9.

    Google Scholar 

  • Hydén, H. (1959). Quantitative assay of compounds in isolated fresh cells from control and stimulated animals. Nature 184:433–435.

    Google Scholar 

  • Hydén, H., Lange, P. W., and Larsson, S. (1980). S100-glia regulation of GABA transport across the nerve cell membrane. J. Neurol. Sci. 45:303–316.

    Google Scholar 

  • Hydén, H., Cupello, A., and Palm, A. (1986). Gamma aminobutyric acid stimulates chloride permeability across microdissected Deiters' neuronal membrane. Brain Res. 379:167–170.

    Google Scholar 

  • Hydén, H., Cupello, A., and Rapallino, M. V. (1999). Chloride permeation across the Deiters' neuron plasma membrane. Activation by GABA on the membrane cytoplasmic side. Neuroscience 89:1391–1400.

    Google Scholar 

  • Ito, M., and Yoshida, M. (1964). The cerebellar-evoked monosynaptic inhibition of Deiters' neurons. Experientia 20:515–516.

    Google Scholar 

  • Ito, M., and Yoshida, M. (1966). The origin of cerebellar-induced inhibition of Deiters neurones. I. Monosynaptic initiation of the inhibitory postsynaptic potentials. Exp. Brain Res. 2:330–349.

    Google Scholar 

  • Ito, M., Kawai, N., Udo, M., and Sato, N. (1968). Cerebellar-evoked disinhibition in dorsal Deiters neurones. Exp. Brain Res. 6:247–264.

    Google Scholar 

  • Jalilian Teherani, M. H., Hablitz, J. J., and Barnes, E. M. (1989). cAMP increases the rate of GABAA receptor desensitization in chick cortical neurons. Synapse 4:126–131.

    Google Scholar 

  • Kataoka, Y., Morii, H., Watanabe, Y., and Ohmori, H. (1997). A postsynaptic excitatory amino acid transporter with chloride conductance functionally regulated by neuronal activity in cerebellar Purkinje cells. J. Neurosci. 17:7017–7024.

    Google Scholar 

  • Kistler, J., Stroud, R. M., Klymkowsky, M. W., Lalancette, R. A., and Fairclough, R. H. (1982). Structure and function of an acetylcholine receptor. Biophys. J. 37:371–383.

    Google Scholar 

  • Larsson, H. P., Picaud, S. A., Werblin, F. S., and Lecar, H. (1996). Noise analysis of the glutamate-activated current in photoreceptors. Biophys. J. 70:733–742.

    Google Scholar 

  • Lauger, P. (1979). A channel mechanism for electrogenic ion pumps. Biochim. Biophys. Acta 552:143–161.

    Google Scholar 

  • Lauger, P. (1983). Conformational transitions of ionic channels. In Sackmann, B., and Neher, E. (eds.), Single Channel Recording, Plenum Press, New York and London, pp. 177–189.

    Google Scholar 

  • Lauger, P. (ed.) (1991). Electrogenic Ionic Pumps, Sinauer, Sunderland, MA, Chap. 2.

    Google Scholar 

  • Obata, K., Ito, M., Ochi, R., and Sato, N. (1967). Pharmacological properties of the postsynaptic inhibition by Purkinje cell axons and the action of γ-aminobutyric acid on Deiters neurons. Exp. Brain Res. 4:43–57.

    Google Scholar 

  • Okada, Y., and Shimada, C. (1976). Gamma-aminobutyric acid (GABA) concentration in a single neuron-localization of GABA in Deiters' neuron. Brain Res. 107:658–662.

    Google Scholar 

  • Rapallino, M. V., Cupello, A., and Hydén, H. (1988). Direct evidence for the presence of GABAA receptors on the cytoplasmic side of the Deiters' neuron membrane. Brain Res. 462:350–353.

    Google Scholar 

  • Rapallino, M. V., Cupello, A., and Hydén, H. (1990). Stimulation of 36Cl− permeation in the in → out direction across the Deiters' neuron membrane by GABA on its cytoplasmic side: Effect of different ionic conditions. Int. J. Neurosci. 53:135–141.

    Google Scholar 

  • Rapallino, M. V., Cupello, A., and Hydén, H. (1992). Further evidence for the presence of GABAA receptors on the cytoplasmic side of Deiters' membrane. Cell. Mol. Neurobiol. 12:327–331.

    Google Scholar 

  • Rapallino, M. V., Cupello, A., and Hydén, H. (1993). The increase in Cl− permeation across the Deiters' neuron membrane by GABA on its cytoplasmic side is abolished by protein kinase C (PKC) activators. Cell. Mol. Neurobiol. 13:547–558.

    Google Scholar 

  • Rattray, M., and Priestley, J. V. (1993). Differential expression of GABA transporter-1 messengers RNA in subpopulations of GABA neurons. Neurosci. Lett. 156:163–166.

    Google Scholar 

  • Risso, S., De Felice, L. J., and Blakely, R. D. (1996). Sodium-dependent GABA-induced currents in GAT1-transfected HeLa cells. J. Physiol. 490:691–702.

    Google Scholar 

  • Robello, M., Amico, C., Bucossi, G., Cupello, A., Rapallino, M. V., and Thellung, S. (1996). Nitric oxide and GABAA receptor function in the rat cerebral cortex and cerebellar granule cells. Neuroscience 74:99–105.

    Google Scholar 

  • Schwiebert, E. M., Morales, M. M., Devidas, S., Egan, M. E., and Guggino, W. B. (1998). Chloride channel and chloride conductance regulator domains of CFTR, the cystic fibrosis transmembrane conductance regulator. Proc. Natl. Acad. Sci. USA 95:2674–2679.

    Google Scholar 

  • Sieghart, W. (1995). Structure and pharmacology of γ-aminobutyric acidA receptor subtypes. Pharm. Rev. 47:182–224.

    Google Scholar 

  • Sigel, E., and Baur, R. (1988). Activation of protein kinase C differentially modulates neuronal Na+, Ca++, and gamma-amino-butyrate type A channels. Proc. Natl. Acad. Sci. USA 85:6192–6196.

    Google Scholar 

  • Sonders, M. S., and Amara, S. G. (1996). Channels in transporters. Curr. Opin. Neurobiol. 6:294–302.

    Google Scholar 

  • Stephenson, F. A. (1995). The GABAA receptors. Biochem. J. 310:1–9.

    Google Scholar 

  • Storm-Mathisen, J. (1975). High affinity uptake of GABA in presumed GABA-ergic nerve endings in rat brain. Brain Res. 84:409–427.

    Google Scholar 

  • Toyoshima, C., and Unwin, N. (1988). Ion channel of acetylcholine receptor reconstructed from images of postsynaptic membranes. Nature 336:247–250.

    Google Scholar 

  • Wadicke, J. I., Amara, S. G., and Kavanaugh, M. P. (1995). Ion fluxes associated with excitatory amino acid transport. Neuron 15:721–728.

    Google Scholar 

  • Wiklund, L., Kunzle, H., and Cuenod, M. (1983). Failure to demonstrate retrograde labelling of cerebellar Purkinje cells after injection of [3H]-GABA in Deiters' nucleus. Neurosci. Lett. 38:23–28.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Centro di Neurofisiologia Cerebrale, CNR, Via De Toni 5, 16132, Genova, Italy

    M. V. Rapallino & A. Cupello

  2. Institute of Neurobiology, University of Goteborg, Goteborg, Sweden

    H. Hydén

Authors
  1. M. V. Rapallino
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Cupello
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H. Hydén
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rapallino, M.V., Cupello, A. & Hydén, H. An Electrogenic Ionic Pump Derived from an Ionotropic Receptor: Assessment of a Candidate. Cell Mol Neurobiol 19, 681–690 (1999). https://doi.org/10.1023/A:1006944820946

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1006944820946

Search

Navigation