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

Vis Neurosci. 1998 Mar-Apr;15(2):257-61. doi: 10.1017/s0952523898152057.

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 1 microM KN-62 or 10 microM 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 microM KN-62 or 10 microM 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / analogs & derivatives
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / pharmacology
  • 1-Methyl-3-isobutylxanthine / pharmacology
  • Ambystoma / growth & development
  • Ambystoma / physiology
  • Animals
  • Benzylamines / pharmacology
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
  • Calcium-Calmodulin-Dependent Protein Kinases / physiology*
  • Cyclic AMP / physiology*
  • Electric Conductivity
  • Enzyme Inhibitors / pharmacology
  • Larva / cytology
  • Phosphodiesterase Inhibitors / pharmacology
  • Retinal Rod Photoreceptor Cells / drug effects
  • Retinal Rod Photoreceptor Cells / physiology*
  • Sulfonamides / pharmacology

Substances

  • Benzylamines
  • Enzyme Inhibitors
  • Phosphodiesterase Inhibitors
  • Sulfonamides
  • KN 93
  • KN 62
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • Cyclic AMP
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium-Calmodulin-Dependent Protein Kinases
  • 1-Methyl-3-isobutylxanthine