The glutamate-receptor linked cGMP cascade of retinal on-bipolar cells is pertussis and cholera toxin-sensitive.
Whole-cell patch-clamp recordings were obtained from light-responsive on-bipolar cells in retinal slices of the dogfish. Inclusion of the A-subunit of pertussis toxin in the patch-pipette solution resulted in an increase in inward current and membrane conductance, and a block of light-evoked currents of on-bipolar cells. The opposite effect was obtained with the A-subunit of cholera toxin, which blocked light responses, and induced an outward current and a decrease in membrane conductance. These actions were NAD+ dependent. The results show that the G-protein(s) linking glutamate receptors to a cGMP cascade in on-bipolar cells possess sites which are ADP-ribosylated by pertussis and cholera toxins, with no homology to the adenylate cyclase system but possibly with a homology to transducin. Furthermore, inclusion of H-7, a kinase inhibitor in the patch-pipette solution, or of a non-hydrolysable ATP analogue (AMP-PNP) had no effect on light responses, membrane conductance or dark current of on-bipolar cells, suggesting that the components of this cGMP cascade are unlikely to be regulated by protein kinases.
Department of Physiology, University College London, U.K.
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Shiells
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Falk
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D037361:Adenylate Cyclase Toxin; D000818:Animals; D002772:Cholera Toxin / Q000494:pharmacology*; D006152:Cyclic GMP / Q000378:metabolism*; D003624:Darkness; D004284:Dogfish; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D046911:Macromolecular Substances; D008564:Membrane Potentials / Q000187:drug effects; D008959:Models, Neurological; D009243:NAD / Q000494:pharmacology; D037342:Pertussis Toxin; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D012160:Retina / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D037361:Adenylate Cyclase Toxin; D007546:Isoquinolines; D046911:Macromolecular Substances; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D010566:Virulence Factors, Bordetella; D009243:NAD; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D002772:Cholera Toxin; D037342:Pertussis Toxin; D006152:Cyclic GMP