Role of guanylate cyclase-activating proteins (GCAPs) in setting the flash sensitivity of rod photoreceptors

Ana Mendez, Marie E Burns, Izabela Sokal, Alexander M. Dizhoor, Wolfgang Baehr, Krzysztof Palczewski, Denis A. Baylor, Jeannie Chen

Research output: Contribution to journalArticle

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Abstract

The retina's photoreceptor cells adjust their sensitivity to allow photons to be transduced over a wide range of light intensities. One mechanism thought to participate in sensitivity adjustments is Ca2+ regulation of guanylate cyclase (GC) by guanylate cyclase-activating proteins (GCAPs). We evaluated the contribution of GCAPs to sensitivity regulation in rods by disrupting their expression in transgenic mice. The GC activity from GCAPs-/- retinas showed no Ca2+ dependence, indicating that Ca2+ regulation of GCs had indeed been abolished. Flash responses from dark-adapted GCAPs-/- rods were larger and slower than responses from wild-type rods. In addition, the incremental flash sensitivity of GCAPs-/- rods failed to be maintained at wild-type levels in bright steady light. GCAP2 expressed in GCAPs-/- rods restored maximal light-induced GC activity but did not restore normal flash response kinetics. We conclude that GCAPs strongly regulate GC activity in mouse rods, decreasing the flash sensitivity in darkness and increasing the incremental flash sensitivity in bright steady light, thereby extending the rod's operating range.

Original languageEnglish (US)
Pages (from-to)9948-9953
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number17
DOIs
StatePublished - Aug 14 2001
Externally publishedYes

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ASJC Scopus subject areas

  • Genetics
  • General

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