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Modulation of the Olfactory CNG Channel by Ptdlns(3,4,5)P3

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Abstract

Recent data suggest that the 3-phosphoinositides can modulate cyclic nucleotide signaling in rat olfactory receptor neurons (ORNs). Given the ability of diverse lipids to modulate ion channels, we asked whether phosphatidylinositol 3,4,5-trisphosphate (PIP3) can regulate the olfactory cyclic nucleotide-gated (CNG) channel as a possible mechanism for this modulation. We show that applying PIP3 to the intracellular side of inside-out patches from rat ORNs inhibits activation of the olfactory CNG channel by cAMP. The effect of PIP3 is immediate and partially reversible, and reflects an increase in the EC50 of cAMP, not a reduction in the single-channel current amplitude. The effect of PIP3 is significantly stronger than that of PIP2; other phospholipids tested have no appreciable effect on channel activity. PIP3 similarly inhibits the recombinant heteromeric (A2/A4) and homomeric (A2) olfactory CNG channel expressed in HEK293 cells, suggesting that PIP3 acts directly on the channel. These findings indicate that 3-phosphoinositides can be functionally important regulators of CNG channels.

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Acknowledgments

We thank Mr. Georgios Sarigiannis for assistance with the experiments. We also thank Dr. R.R. Reed and Dr. J. Bradley (Johns Hopkins School of Medicine, Baltimore, MD) for the CNGA2 and CNGA4 clones. This work was supported by grants from the NIDCD (BWA and ABZ), the DFG (HH), and the AvH Stiftung.

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Authors and Affiliations

  1. Whitney Laboratory, Center for Smell and Taste, McKnight Brain Institute, University of Florida, Gainesville, FL, 32610, USA

    A.B. Zhainazarov & B.W. Ache

  2. Dept. of Cell Physiology, Ruhr University, Bochum, Bochum, 44780, Germany

    M. Spehr, C.H. Wetzel & H. Hatt

  3. Depts. of Zoology and Neuroscience, University of Florida, Gainesville, FL, 32610, USA

    B.W. Ache

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  1. A.B. Zhainazarov
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  2. M. Spehr
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Correspondence to A.B. Zhainazarov.

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Zhainazarov, A., Spehr, M., Wetzel, C. et al. Modulation of the Olfactory CNG Channel by Ptdlns(3,4,5)P3 . J Membrane Biol 201, 51–57 (2004). https://doi.org/10.1007/s00232-004-0707-4

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  • DOI: https://doi.org/10.1007/s00232-004-0707-4

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