A Transient Receptor Potential-Like Channel Mediates Synaptic Transmission in Rod Bipolar Cells

Shen, Yin; Heimel, J. Alexander; Kamermans, Maarten; Peachey, Neal S.; Gregg, Ronald G.; Nawy, Scott

doi:10.1523/jneurosci.0132-09.2009

Cited by 192 publications

(239 citation statements)

References 35 publications

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“…The currentvoltage (I-V) relationship that was suppressed by capsazepine displayed a strong outward rectification (Fig. 2E), comparable to that obtained previously in RBCs (2). These results are consistent with the idea that, capsazepine acts to inhibit the activity of constitutively open TRPM1 channels, although the mechanism for such inhibition is unclear.…”

Section: Resultssupporting

confidence: 90%

“…As expected, application of LY341495 did not produce a detectable response in RBCs ( Fig. 2A, Left), as mGluR6 transduction is absent in this mouse model (2)(3)(4). Moreover, we were unable to detect responses to capsaicin in RBCs from trpm1 tm1Lex mice ( Fig.…”

Section: Resultssupporting

confidence: 71%

“…1D illustrates the response of an RBC to a 10-ms full-field flash of 425 nm light delivering 3.6 photons/µm 2 , a flash strength that will activate only rods (21)(22)(23). At a concentration of 10 nM, dialysis of Gβγ resulted in a slow depression of the light response, reaching a steady-state value of 39.0 ± 6.5 of the response at break-in after 10 min of dialysis, ( (2). As a further test of this idea, we measured responses to capsaicin as well as LY341495 in mice lacking functional TRPM1 channels (trpm1 tm1Lex ).…”

Section: Resultsmentioning

confidence: 99%

“…We have previously suggested that capsazepine also antagonizes TRPM1 current in RBCs, and that capsaicin acts as an agonist (2). Recently Morgans et al (3) reported a 50% reduction in the average response to capsaicin in ON bipolar cells of trpm1 tm1Lex mice compared with wild type, but not complete elimination of the response.…”

Section: Discussionmentioning

confidence: 97%

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G-protein–mediated inhibition of the Trp channel TRPM1 requires the Gβγ dimer

Shen

Rampino

Carroll

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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ON bipolar cells are critical for the function of the ON pathway in the visual system. They express a metabotropic glutamate receptor (mGluR6) that, when activated, couples to the G o class of G protein. The channel that is primarily responsible for the synaptic response has been recently identified as the transient receptor potential cation channel subfamily M member 1 (TRPM1); TRPM1 is negatively coupled to the mGluR6/Go cascade such that activation of the cascade results in closure of the channel. Light indirectly opens TRPM1 by reducing transmitter release from presynaptic photoreceptors, resulting in a decrease in mGluR6 activation. Conversely, in the dark, binding of synaptic glutamate to mGluR6 inhibits TRPM1 current. Closure of TRPM1 by G-protein activation in the dark is a critical step in the process of ON bipolar cell signal transduction, but the precise pathway linking these two events is not understood. To address this question, we measured TRPM1 activity in retinal bipolar cells, in human ependymal melanocytes (HEMs) that endogenously express TRPM1, and in HEK293 cells transfected with TRPM1. Dialysis of the Gβγ subunit dimer, but not Gα o , closed TRPM1 channels in every cell type that we tested. In addition, activation of an endogenous G-protein-coupled receptor pathway in HEK293 cells that releases Gβγ without activating Go protein also closed TRPM1 channels. These results suggest a model in which the Gβγ dimer that is released as a result of the dissociation from Gα o upon activation of mGluR6 closes the TRPM1 channel, perhaps via a direct interaction. patch clamp | calcium imaging R etinal ON bipolar cells are connected to photoreceptors through a sign-inverting synapse. At this synapse, glutamate binds to the metabotropic glutamate receptor mGluR6, which couples to the closure of a cation-selective transduction channel. Insight into the molecular identity of the transduction channel was gained from the observation that low levels of mRNA encoding the transient receptor potential ion channel TRPM1 was associated with a form of congenital stationary night blindness (CSNB) in a population of Appaloosa horses (1). Soon after, it was shown that ON bipolar cell function was absent or severely impaired in a mouse model that lacked TRPM1 expression (2-4), although there is evidence that one or more classes of cone-driven ON bipolar cells may use an additional channel (3). Mutations in TRPM1 have now been positively linked to CSNB in humans as well (5-7). Taken together, studies of mouse, horse, and human provide convincing evidence that the ON bipolar cell transduction channel is composed of TRPM1, either alone or in conjunction with other channels. However, all these studies do not provide insight into the mechanism by which activation of mGluR6 leads to closure of TRPM1.The metabotropic receptor mGluR6 preferentially couples to the G o class of G protein, both in bipolar cells (8, 9) and expression systems (10, 11). Activation of mGluR6 and, correspondingly, Go, results in closure of TRPM1. However...

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Section: Resultssupporting

confidence: 90%

Section: Resultssupporting

confidence: 71%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 97%

See 2 more Smart Citations

G-protein–mediated inhibition of the Trp channel TRPM1 requires the Gβγ dimer

Shen

Rampino

Carroll

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…It encodes the transient receptor potential cation channel M1, a calcium permeable cation channel that mediates synaptic transmission from photoreceptors to ON bipolar cells, promoting a change in the membrane potential that results in the light-evoked response of the ON bipolar cells. 33 Mutations in the TRPM1 gene have been identified as an important cause of autosomal-recessive complete congenital stationary night blindness in humans. 34 Importantly, Fejgin et al have recently generated the first mouse model of the human 15q13.3 microdeletion syndrome (Df[h15q13]/ þ ) by hemizigous deletion of the orthologous genomic region on mouse chromosome 7.…”

Section: Mutational Spectrummentioning

confidence: 99%