Visual Neuroscience

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

R.J.  WALTERS a1, R.H.  KRAMER a2 and S.  NAWY a1c1
a1 Department of Ophthalmology and Visual Science, Albert Einstein College of Medicine, Bronx
a2 Department of Molecular and Cellular Pharmacology, University of Miami School of Medicine, Miami


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 [mu]M KN-62 or 10 [mu]M 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 [mu]M KN-62 or 10 [mu]M 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.

(Received March 20 1997)
(Accepted September 22 1997)

Key Words: On bipolar cell; KN-62; KN-93; mGluR6 receptor; L-2-amino-4-phosphonobutyrate.

c1 Reprint requests to: Scott Nawy, Department of Ophthalmology and Visual Science, 1300 Morris Park Avenue, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.