Regulation of cGMP-dependent current in on bipolar cells by calcium/calmodulin-dependent kinase

R. J. Walters, R. H. Kramer, Scott Nawy

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

The metabotropic receptor mGluR6 is localized to the dendrites of On bipolar cells and mediates synaptic input from photoreceptors. The binding of glutamate to the receptor activates a phosphodiesterase (PDE), which then hydrolyzes cGMP. A nonselective cationic conductance, believed to be gated directly by cGMP, is turned off as a result of the fall in cGMP levels, and the cell hyperpolarizes. Here we present evidence for regulation of the conductance by an additional mechanism that it is independent of cGMP. Whole-cell recordings were obtained from On bipolar cells in slices of tiger salamander retina. Dialysis of cells with I μM KN-62 or 10 μM KN-93, two inhibitors of type II calmodulin-dependent protein kinase (CaMKII), depressed cGMP-dependent currents. This depression persisted when hydrolysis of cGMP was prevented with IBMX, a broad-spectrum PDE inhibitor, suggesting that CaMKII acts downstream from the PDE in the cascade. The depression of cGMP-dependent currents was probably not due to a direct interaction of the inhibitors with the channels as neither 1 μM KN-62 or 10 μM KN-93 was found to have any effect on cyclic nucleotide-gated channels when applied directly to excised patches of rod outer segments. We propose that phosphorylation by CaMKII may be an important mechanism for regulating the cGMP-dependent conductance of On bipolar cells.

Original languageEnglish (US)
Pages (from-to)257-261
Number of pages5
JournalVisual Neuroscience
Volume15
Issue number2
DOIs
StatePublished - Mar 1 1998

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Calcium-Calmodulin-Dependent Protein Kinases
Calcium-Calmodulin-Dependent Protein Kinase Type 2
KN 62
Calcium
Phosphoric Diester Hydrolases
Cyclic Nucleotide-Gated Cation Channels
Ambystoma
Rod Cell Outer Segment
1-Methyl-3-isobutylxanthine
Phosphodiesterase Inhibitors
Glutamate Receptors
Patch-Clamp Techniques
Dendrites
Retina
Dialysis
Hydrolysis
Phosphorylation

Keywords

  • KN-62
  • KN-93
  • L-2-amino-4-phosphonobutyrate
  • On bipolar cell
  • mGluR6 receptor

ASJC Scopus subject areas

  • Physiology
  • Sensory Systems

Cite this

Regulation of cGMP-dependent current in on bipolar cells by calcium/calmodulin-dependent kinase. / Walters, R. J.; Kramer, R. H.; Nawy, Scott.

In: Visual Neuroscience, Vol. 15, No. 2, 01.03.1998, p. 257-261.

Research output: Contribution to journalArticle

Walters, R. J. ; Kramer, R. H. ; Nawy, Scott. / Regulation of cGMP-dependent current in on bipolar cells by calcium/calmodulin-dependent kinase. In: Visual Neuroscience. 1998 ; Vol. 15, No. 2. pp. 257-261.
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