Regulation of the retinal bipolar cell mGluR6 pathway by calcineurin

Josefin Snellman, Scott Nawy

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

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 (Iglu) with whole cell recordings of ON bipolar cells in light-adapted retinal slices. Depression of Iglu 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 Iglu was restored. Similarly, CaN420 induced depression of Iglu during continuous glutamate application, a protocol that ordinarily prevents depression. Analysis of changes in the amplitude of the cation-selective current (Icat) of cells that were dialyzed with high Ca2+ (1 μM), or with BAPTA and CaN420, indicates that Ca2+ depresses Iglu by reducing Icat and that calcineurin acts via the same mechanism. Ca2+-mediated depression of Iglu 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.

Original languageEnglish (US)
Pages (from-to)1088-1096
Number of pages9
JournalJournal of Neurophysiology
Volume88
Issue number3
DOIs
StatePublished - Sep 2002

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology

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