Send to

Choose Destination
J Physiol. 2003 Jun 15;549(Pt 3):787-800. Epub 2003 May 2.

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

Author information

Basic Neurosciences Program, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.


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.

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center