Modulation of the synaptic Ca2+ current in salamander photoreceptors by polyunsaturated fatty acids and retinoids.
Synaptic transmission between retinal photoreceptors and second-order neurones is controlled by an L-type Ca2+ conductance (gCa) in the photoreceptor inner segment. Modulation of this conductance therefore influences the flow of visual information to higher centres. Possible modulation of gCa by retinal factors was investigated using patch clamp and Ca2+ imaging. No significant modulation of gCa by retinal neurotransmitters nor by intracellular signalling pathways was found. gCa was inhibited by retinoids (all-trans retinal) and by polyunsaturated fatty acids (PUFAs) such as arachidonic acid and docosahexaenoic acid, which are known to be released in the retina by exposure to light. Some PUFAs tested are physiological substrates for the cyclo-oxygenase, lipoxygenase and epoxygenase pathways, but specific inhibitors of these pathways had no effect on the inhibition of gCa. Treatments designed to activate or inhibit G-protein-coupled pathways or protein kinases A and C similarly had no effect on the inhibition by PUFAs nor on gCa itself. Inhibitors of phosphatases 1 and 2A were also largely ineffective. The inhibition by PUFAs is, however, dependent on membrane potential, suggesting that it arises from a direct interaction of fatty acids with the Ca2+ channel. The effect was not use or frequency dependent, suggesting that the effect does not depend on channel gating state. Control by retinoids and by PUFAs may be an important mechanism by which the Ca2+ conductance, and consequently the transmission of the visual signal, is modulated at the first retinal synapse.
Vellani
V
V
Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QJ, UK.
Reynolds
A M
AM
McNaughton
P A
PA
D000221:Adaptation, Ocular; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D000090762:Cytochrome P-450 CYP2J2; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System; D004553:Electric Conductivity; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000502:physiology; D008564:Membrane Potentials; D018377:Neurotransmitter Agents / Q000494:pharmacology; D010105:Oxygenases / Q000037:antagonists & inhibitors; D018408:Patch-Clamp Techniques; D010749:Phosphoprotein Phosphatases / Q000502:physiology; D011494:Protein Kinases / Q000502:physiology; D017948:Retinal Rod Photoreceptor Cells / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D012176:Retinoids / Q000494:pharmacology*; D009435:Synaptic Transmission; D014562:Caudata
D015220:Calcium Channels; D016861:Cyclooxygenase Inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D005231:Fatty Acids, Unsaturated; D018377:Neurotransmitter Agents; D012176:Retinoids; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; D000090762:Cytochrome P-450 CYP2J2; D011494:Protein Kinases; D010749:Phosphoprotein Phosphatases; D019204:GTP-Binding Proteins