The Journal of Neurophysiology Vol. 88 No. 3 September 2002, pp. 1088-1096
Copyright ©2002 by the American Physiological Society

Regulation of the Retinal Bipolar Cell mGluR6 Pathway by Calcineurin

Departments of Ophthalmology and Visual Science, and Neuroscience, Albert Einstein College of Medicine, Bronx, NewYork 10461

Snellman, Josefin and Scott Nawy. Regulation of the Retinal Bipolar Cell mGluR6 Pathway by Calcineurin. J. Neurophysiol. 88: 1088-1096, 2002. Glutamate produces a hyperpolarizing postsynaptic potential in ON bipolar cells by binding to the metabotropic receptor mGluR6 and subsequently closing a cation-selective channel. It has been proposed that Ca²⁺ influx through the cation channel triggers a depression of the synaptic potential. Here we report that this Ca²⁺-mediated depression requires activation of calcineurin, a Ca²⁺/calmodulin-regulated phosphatase. We measured glutamate-evoked currents (I_glu) with whole cell recordings of ON bipolar cells in light-adapted retinal slices. Depression of I_glu by Ca²⁺ was prevented by inhibitors of calcineurin or by tightly buffering Ca²⁺ with bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA). However, when cells were dialyzed with BAPTA and a Ca²⁺-independent form of calcineurin (CaN420), depression of I_glu was restored. Similarly, CaN420 induced depression of I_glu during continuous glutamate application, a protocol that ordinarily prevents depression. Analysis of changes in the amplitude of the cation-selective current (I_cat) of cells that were dialyzed with high Ca²⁺ (1 µM), or with BAPTA and CaN420, indicates that Ca²⁺ depresses I_glu by reducing I_cat and that calcineurin acts via the same mechanism. Ca²⁺-mediated depression of I_glu was not found to involve CaMKII, as inhibitors of CaMKII did not prevent this depression nor did they affect the sensitivity of the response to small changes in the concentration of mGluR6 agonist. Our data suggest that Ca²⁺ and calcineurin may play an adaptive role at the synapse between photoreceptor and ON bipolar cells, closing postsynaptic cation channels that are opened by a drop in synaptic glutamate levels during prolonged photoreceptor illumination.