Stimulation of sodium pump restores membrane potential to neurons excited by glutamate in zebrafish distal retina

J Physiol. 2003 Jun 15;549(Pt 3):787-800. doi: 10.1113/jphysiol.2003.042051. Epub 2003 May 2.

Abstract

Glutamate either depolarizes or hyperpolarizes retinal neurons. Those are the initial and primary effects. Using a voltage probe (oxonol, DiBaC4 (5)) to study dissociated zebrafish retinal neurons, we find a secondary, longer-term effect: a post-excitatory restoration of membrane potential, termed after-hyperpolarization (AHP). AHP occurs only in neurons that are depolarized by glutamate and typically peaks about 5 min after glutamate application. AHP is seen in dissociated horizontal cells (HCs) and hyperpolarizing, or OFF type, bipolar cells (HBCs). These cells commonly respond with only an AHP component. AHP never occurs in depolarizing, or ON type, bipolar cells (DBCs), which are cell types hyperpolarized by glutamate. AHP is blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). It is evoked by kainate, AMPA and the AMPA-selective agonist (S)-5-fluorowillardiine, but not by NMDA, D-aspartate, the kainate-selective agonist SYM 2081 or by DL-2-amino-4-phosphonobutyric acid (DL-AP4). Cells with exclusively AHP responses are tonically depolarized. Resting potentials can be restored by nifedipine, suggesting a tonic, depolarizing action of L-type Ca2+ channels. However AHP is not blocked by nifedipine and is insensitive to [Cl-]o. AHP is blocked by Li+o substitution for Na+o and by ouabain. A mechanism is proposed in which Na+ entering through ionotropic AMPA channels stimulates Na+,K+-ATPase, which, by electrogenic action, restores membrane potential, generating the AHP response. Patterns of ATPase immunoreactivity support localization in the outer plexiform layer (OPL) as cone pedicles, HCs and BCs were positively labelled. Labelling was weaker in the inner plexiform layer (IPL) than in nuclear layers, though two IPL bands of immunoreactive BC terminals could be discerned, one in sublamina a and the other in sublamina b. Persistent stimulation of distal retina by photoreceptor glutamate may induce increased expression and activity of Na+,K+-ATPase, with a consequent impact on distal glutamate responses.

MeSH terms

  • 6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
  • Animals
  • Calcium Channels, L-Type / metabolism
  • Calcium Channels, L-Type / physiology
  • Calibration
  • Chlorides / metabolism
  • Electric Stimulation
  • Enzyme Inhibitors / pharmacology
  • Excitatory Amino Acid Agonists / pharmacology*
  • Excitatory Amino Acid Antagonists / pharmacology
  • Glutamic Acid / pharmacology*
  • Immunohistochemistry
  • Interneurons / drug effects
  • Interneurons / metabolism
  • Ion Channel Gating / drug effects
  • Membrane Potentials / drug effects*
  • Neurons / drug effects
  • Neurons / metabolism*
  • Ouabain / pharmacology
  • Potassium Channels / drug effects
  • Potassium Channels / metabolism
  • Receptors, Glutamate / drug effects
  • Retina / cytology
  • Retina / drug effects
  • Retina / metabolism*
  • Sodium Channels / drug effects
  • Sodium Channels / metabolism
  • Sodium-Potassium-Exchanging ATPase / antagonists & inhibitors
  • Sodium-Potassium-Exchanging ATPase / metabolism*
  • Stimulation, Chemical
  • Zebrafish / physiology*

Substances

  • Calcium Channels, L-Type
  • Chlorides
  • Enzyme Inhibitors
  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • Potassium Channels
  • Receptors, Glutamate
  • Sodium Channels
  • Glutamic Acid
  • Ouabain
  • 6-Cyano-7-nitroquinoxaline-2,3-dione
  • Sodium-Potassium-Exchanging ATPase