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Do phosphatidylinositides modulate vertebrate phototransduction?
- Source :
-
The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2000 Apr 15; Vol. 20 (8), pp. 2792-9. - Publication Year :
- 2000
-
Abstract
- Mammalian rod cyclic nucleotide gated (CNG) channels (i.e., alpha plus beta subunits) are strongly inhibited by phosphatidylinositol 4, 5-bisphosphate (PIP(2)) when they are expressed in Xenopus oocytes and studied in giant membrane patches. Cytoplasmic Mg-ATP inhibits CNG currents similarly, and monoclonal antibodies to PIP(2) reverse the effect and hyperactivate currents. When alpha subunits are expressed alone, PIP(2) inhibition is less strong; olfactory CNG channels are not inhibited. In giant patches from rod outer segments, inhibition by PIP(2) is intermediate. Other anionic lipids (e.g., phosphatidyl serine and phosphatidic acid), a phosphatidylinositol-specific phospholipase C, and full-length diacylglycerol have stimulatory effects. Although ATP also potently inhibits cGMP-activated currents in rod patches, the following findings indicate that ATP is used to transphosphorylate GMP, generated from cGMP, to GTP. First, a phosphodiesterase (PDE) inhibitor, Zaprinast, blocks inhibition by ATP. Second, inhibition can be rapidly reversed by exogenous regulator of G-protein signaling 9, suggesting G-protein activation by ATP. Third, the reversal of ATP effects is greatly slowed when cyclic inosine 5'-monophosphate is used to activate currents, as expected for slow inosine 5' triphosphate hydrolysis by G-proteins. Still, other results remain suggestive of regulatory roles for PIP(2). First, the cGMP concentration producing half-maximal CNG channel activity (K(1/2)) is decreased by PIP(2) antibody in the presence of PDE inhibitors. Second, the activation of PDE activity by several nucleotides, monitored electrophysiologically and biochemically, is reversed by PIP(2) antibody. Third, exogenous PIP(2) can enhance PDE activation by nucleotides.
- Subjects :
- Adenosine Triphosphate physiology
Animals
Cattle
Cyclic GMP metabolism
Cyclic IMP metabolism
Cyclic Nucleotide-Gated Cation Channels
Diacylglycerol Kinase pharmacology
Diacylglycerol Kinase physiology
Guanosine Triphosphate physiology
Ion Channels drug effects
Ion Channels physiology
Patch-Clamp Techniques
Phosphatidylinositol 4,5-Diphosphate physiology
Phosphotransferases pharmacology
Phosphotransferases physiology
RGS Proteins physiology
Retinal Rod Photoreceptor Cells physiology
Vision, Ocular physiology
Xenopus
Adenosine Triphosphate pharmacology
Guanosine Triphosphate pharmacology
Phosphatidylinositol 4,5-Diphosphate pharmacology
RGS Proteins pharmacology
Retinal Rod Photoreceptor Cells drug effects
Vision, Ocular drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1529-2401
- Volume :
- 20
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- The Journal of neuroscience : the official journal of the Society for Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 10751430