A transient receptor potential-like channel mediates synaptic transmission in rod bipolar cells.
On bipolar cells are connected to photoreceptors via a sign-inverting synapse. At this synapse, glutamate binds to a metabotropic receptor which couples to the closure of a cation-selective transduction channel. The molecular identity of both the receptor and the G protein are known, but the identity of the transduction channel has remained elusive. Here, we show that the transduction channel in mouse rod bipolar cells, a subtype of On bipolar cell, is likely to be a member of the TRP family of channels. To evoke a transduction current, the metabotropic receptor antagonist LY341495 was applied to the dendrites of cells that were bathed in a solution containing the mGluR6 agonists L-AP4 or glutamate. The transduction current was suppressed by ruthenium red and the TRPV1 antagonists capsazepine and SB-366791. Furthermore, focal application of the TRPV1 agonists capsaicin and anandamide evoked a transduction-like current. The capsaicin-evoked and endogenous transduction current displayed prominent outward rectification, a property of the TRPV1 channel. To test the possibility that the transduction channel is TRPV1, we measured rod bipolar cell function in the TRPV1(-/-) mouse. The ERG b-wave, a measure of On bipolar cell function, as well as the transduction current and the response to TRPV1 agonists were normal, arguing against a role for TRPV1. However, ERG measurements from mice lacking TRPM1 receptors, another TRP channel implicated in retinal function, revealed the absence of a b-wave. Our results suggest that a TRP-like channel, possibly TRPM1, is essential for synaptic function in On bipolar cells.
Shen
Yin
Y
Department of Ophthalmology, Albert Einstein College of Medicine, Bronx, New York 10461, USA. yshen@aecom.yu.edu
Heimel
J Alexander
JA
Kamermans
Maarten
M
Peachey
Neal S
NS
Gregg
Ronald G
RG
Nawy
Scott
S
D000596:Amino Acids / Q000494:pharmacology; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D002934:Cinnamates / Q000494:pharmacology; D063388:Endocannabinoids; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053284:Polyunsaturated Alkamides / Q000494:pharmacology; D011422:Propionates / Q000494:pharmacology; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000378:metabolism; D051245:Retinal Bipolar Cells / Q000502:physiology*; D012430:Ruthenium Red / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D050053:TRPM Cation Channels / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D050916:TRPV Cation Channels / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D050051:Transient Receptor Potential Channels / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014966:Xanthenes / Q000494:pharmacology
C114785:2-amino-4-phosphono-propinate; D000596:Amino Acids; D000813:Anilides; D001095:Arachidonic Acids; D002934:Cinnamates; D063388:Endocannabinoids; D018691:Excitatory Amino Acid Antagonists; C114624:LY 341495; C477659:N-(3-methoxyphenyl)-4-chlorocinnamanilide; D053284:Polyunsaturated Alkamides; D011422:Propionates; D018094:Receptors, Metabotropic Glutamate; D050053:TRPM Cation Channels; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D050051:Transient Receptor Potential Channels; C116297:Trpm1 protein, mouse; D014966:Xanthenes; C113897:metabotropic glutamate receptor 6; D012430:Ruthenium Red; D018698:Glutamic Acid; C071423:capsazepine; D002211:Capsaicin; C078814:anandamide