Skip to main content
×
Home
    • Aa
    • Aa

Multiple functions of cation-chloride cotransporters in the fish retina

  • ANDREY V. DMITRIEV (a1), NINA A. DMITRIEVA (a2) (a3), KENT T. KEYSER (a3) and STUART C. MANGEL (a1)
Abstract

A GABA- or glycine-induced increase in Cl permeability can produce either a depolarization or hyperpolarization, depending on the Cl equilibrium potential. It has been shown that retinal neurons express the chloride cotransporters, Na-K-2Cl (NKCC) and K-Cl (KCC), the primary molecular mechanisms that control the intracellular Cl concentration. We thus studied (1) the localization of these cotransporters in the fish retina, and (2) how suppression of cotransporter activity in the fish retina affects function. Specific antibodies against NKCC and KCC2 revealed that both cotransporters were expressed in the outer and inner plexiform layers, and colocalized in many putative amacrine cells and in cells of the ganglion cell layer. However, the somata of putative horizontal cells displayed only NKCC immunoreactivity and many bipolar cells were only immunopositive for KCC2. In the outer retina, application of bumetanide, a specific inhibitor of NKCC activity, (1) increased the steady-state extracellular concentration of K+ ([K+]o) and enhanced the light-induced decrease in the [K+]o, (2) increased the sPIII photoreceptor-dependent component of the ERG, and (3) reduced the extracellular space volume. In contrast, in the outer retina, application of furosemide, a specific inhibitor of KCC activity, decreased sPIII and the light-induced reduction in [K+]o, but had little effect on steady-state [K+]o. In the inner retina, bumetanide increased the sustained component of the light-induced increase in [K+]o. These findings thus indicate that NKCC and KCC2 control the [K+]o and extracellular space volume in the retina in addition to regulating GABA- and glycine-mediated synaptic transmission. In addition, the anatomical and electrophysiological results together suggest that all of the major neuronal types in the fish retina are influenced by chloride cotransporter activity.

Copyright
Corresponding author
Address correspondence and reprint requests to: Stuart Mangel, Department of Neuroscience, The Ohio State University College of Medicine, 333 West 10th Avenue, Columbus, OH 43210. E-mail: mangel.1@osu.edu
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

Dmitriev, A.V., Govardovskii, V.I., Schwahn, H.N. & Steinberg R.H. (1999). Light-induced changes of extracellular ions and volume in the isolated chick retina-pigment epithelium preparation. Visual Neuroscience 16, 11571167.

Gamba, G. (2005). Molecular physiology and pathophysiology of electroneutral cation-chloride cotransporters. Physiological Reviews 85, 423493.

Gavrikov, K.E., Dmitriev, A.V., Keyser, K.T. & Mangel, S.C. (2003). Cation-chloride cotransporters mediate neural computation in the retina. Proceedings of the National Academy of Sciences of the USA 100, 1604716052.

Gavrikov, K.E., Nilson, J.E., Dmitriev, A.V., Zucker, C.L. & Mangel S.C. (2006). Dendritic compartmentalization of chloride cotransporters underlies directional responses of starburst amacrine cells in retina. Proceedings of the National Academy of Sciences of the USA 103, 1879318798.

Hanitzsch, R. (1973). Intraretinal isolation of P3 subcomponents in the isolated rabbit retina after treatment with sodium aspartate. Vision Research 13, 20932102.

Kuffler, S.W. (1967). Neuroglial cells: Physiological properties and a potassium mediated effect on the glial membrane potential. Proceedings of the Royal Society. B, Biological Sciences 168, 121.

Maksay, G., Korpi, E.R. & Uusi-Oukari, M. (1998). Bimodal action of furosemide on convulsant [3H] EBOB binding to cerebellar and cortical GABAA receptors. Neurochemistry International 33, 353358.

Miller, R.F. & Dacheux, R.F. (1976). Synaptic organization and ionic basis of On and Off channels in mudpuppy retina. I. Intracellular analysis of chloride-sensitive electrogenic properties of receptors, horizontal cells, bipolar cells, and amacrine cell. Journal of General Physiology 67, 639659.

Miller, R.F. & Dacheux, R.F. (1983). Intracellular chloride in retinal neurons: Measurement and meaning. Vision Research 23, 399411.

Nicholson, C. & Sykova, E. (1998). Extracellular space structure revealed by diffusion analysis. Trends in Neurosciences 21, 207215.

Payne, J.A., Rivera, C., Voipio, J. & Kaila, K. (2003). Cation-chloride co-transporters in neuronal communication, development and trauma. Trends in Neurosciences 26, 199206.

Williams, J.R., Sharp, J.W., Kumari, V.G., Wilson, M. & Payne, J.A. (1999). The neuron-specific K-Cl cotransporter, KCC2. Journal of Biological Chemistry 274, 1265612664.

Witkovsky, P., Dudek, F.E. & Ripps, H. (1975). Slow PIII component of the carp electroretinogram. Journal of General Physiology 65, 119134.

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Visual Neuroscience
  • ISSN: 0952-5238
  • EISSN: 1469-8714
  • URL: /core/journals/visual-neuroscience
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Keywords:

Metrics

Full text views

Total number of HTML views: 2
Total number of PDF views: 5 *
Loading metrics...

Abstract views

Total abstract views: 93 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 28th May 2017. This data will be updated every 24 hours.