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Article ; Online: Hydrogen Peroxide Affects the Electroretinogram of Isolated Perfused Rat Retina.

Jacquemot, Nathalie / Wersinger, Eric / Brabet, Philippe / Cia, David

2023 Volume 48, Issue 12, Page(s) 1179–1188

Abstract: Purpose: To evaluate the effects of H: Methods: Retinas were isolated from rat eyes and perfused with a nutrient solution. ERGs were recorded every 3 min. Once the signal was at a steady state, H: Results: H: Conclusions: ... ...

Abstract	Purpose: To evaluate the effects of H Methods: Retinas were isolated from rat eyes and perfused with a nutrient solution. ERGs were recorded every 3 min. Once the signal was at a steady state, H Results: H Conclusions: H
MeSH term(s)	Rats ; Animals ; Hydrogen Peroxide/pharmacology ; Barium/pharmacology ; Retina ; Electroretinography
Chemical Substances	Hydrogen Peroxide (BBX060AN9V) ; Barium (24GP945V5T)
Language	English
Publishing date	2023-09-14
Publishing country	England
Document type	Journal Article
ZDB-ID	82079-9
ISSN	1460-2202 ; 0271-3683
ISSN (online)	1460-2202
ISSN	0271-3683
DOI	10.1080/02713683.2023.2256029
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Zs.A 1775: Show issues

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Article ; Online: Evidence for functional GABAA but not GABAC receptors in mouse cone photoreceptors.

Deniz, Sercan / Wersinger, Eric / Picaud, Serge / Roux, Michel J

Visual neuroscience

2019 Volume 36, Page(s) E005

Abstract: At the first retinal synapse, horizontal cells (HCs) contact both photoreceptor terminals and bipolar cell dendrites, modulating information transfer between these two cell types to enhance spatial contrast and mediate color opponency. The synaptic ... ...

Abstract	At the first retinal synapse, horizontal cells (HCs) contact both photoreceptor terminals and bipolar cell dendrites, modulating information transfer between these two cell types to enhance spatial contrast and mediate color opponency. The synaptic mechanisms through which these modulations occur are still debated. The initial hypothesis of a GABAergic feedback from HCs to cones has been challenged by pharmacological inconsistencies. Surround antagonism has been demonstrated to occur via a modulation of cone calcium channels through ephaptic signaling and pH changes in the synaptic cleft. GABAergic transmission between HCs and cones has been reported in some lower vertebrates, like the turtle and tiger salamander. In these reports, it was revealed that GABA is released from HCs through reverse transport and target GABA receptors are located at the cone terminals. In mammalian retinas, there is growing evidence that HCs can release GABA through conventional vesicular transmission, acting both on autaptic GABA receptors and on receptors expressed at the dendritic tips of the bipolar cells. The presence of GABA receptors on mammalian cone terminals remains equivocal. Here, we looked specifically for functional GABA receptors in mouse photoreceptors by recording in the whole-cell or amphotericin/gramicidin-perforated patch clamp configurations. Cones could be differentiated from rods through morphological criteria. Local GABA applications evoked a Cl- current in cones but not in rods. It was blocked by the GABAA receptor antagonist bicuculline methiodide and unaffected by the GABAC receptor antagonist TPMPA [(1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid]. The voltage dependency of the current amplitude was as expected from a direct action of GABA on cone pedicles but not from an indirect modulation of cone currents following the activation of the GABA receptors of HCs. This supports a direct role of GABA released from HCs in the control of cone activity in the mouse retina.
MeSH term(s)	Animals ; GABA Antagonists/pharmacology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Patch-Clamp Techniques ; Receptors, GABA/drug effects ; Receptors, GABA/metabolism ; Receptors, GABA-A/drug effects ; Receptors, GABA-A/metabolism ; Retinal Cone Photoreceptor Cells/metabolism ; Retinal Cone Photoreceptor Cells/physiology ; Retinal Horizontal Cells/metabolism ; gamma-Aminobutyric Acid/metabolism
Chemical Substances	GABA Antagonists ; GABA-C receptor ; Receptors, GABA ; Receptors, GABA-A ; gamma-Aminobutyric Acid (56-12-2)
Language	English
Publishing date	2019-06-14
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639436-x
ISSN	1469-8714 ; 0952-5238
ISSN (online)	1469-8714
ISSN	0952-5238
DOI	10.1017/S0952523819000038
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Zs.A 2359: Show issues

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Article ; Online: Effect of the novel histamine H

Petremann, Mathieu / Gueguen, Cindy / Delgado Betancourt, Viviana / Wersinger, Eric / Dyhrfjeld-Johnsen, Jonas

British journal of pharmacology

2019 Volume 177, Issue 3, Page(s) 623–633

Abstract: Background and purpose: Histamine H: Experimental approach: Pharmacokinetics of SENS-111 in rats was determined to aid dose selection for efficacy testing. Vestibular lesions were induced in rats by unilateral transtympanic injection of kainic acid. ... ...

Abstract	Background and purpose: Histamine H Experimental approach: Pharmacokinetics of SENS-111 in rats was determined to aid dose selection for efficacy testing. Vestibular lesions were induced in rats by unilateral transtympanic injection of kainic acid. The effect of SENS-111 (10 or 20 mg·kg Key results: Doses were selected for plasma exposure were consistent with published phase 1 results from healthy volunteers. SENS-111 of 10 mg·kg Conclusions and implications: The exposure-efficacy relationship for improved spontaneous nystagmus seen with SENS-111 in this in vivo model is consistent with phase 1 clinical results and provides preclinical support for pharmacokinetic/pharmacodynamic modelling and selection of effective clinical drug concentrations. Linked articles: This article is part of a themed section on New Uses for 21st Century. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.3/issuetoc.
MeSH term(s)	Animals ; Azetidines ; Histamine ; Histamine Antagonists/pharmacology ; Pyrimidines ; Rats
Chemical Substances	Azetidines ; Histamine Antagonists ; Pyrimidines ; seliforant ; Histamine (820484N8I3)
Language	English
Publishing date	2019-08-28
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80081-8
ISSN	1476-5381 ; 0007-1188
ISSN (online)	1476-5381
ISSN	0007-1188
DOI	10.1111/bph.14803
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Uf I Zs.146: Show issues

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Article ; Online: Safety, tolerability, pharmacokinetics and pharmacokinetic-pharmacodynamic modelling of the novel H

Venail, Frédéric / Attali, Pierre / Wersinger, Eric / Gomeni, Roberto / Poli, Sonia / Schmerber, Sebastien

British journal of clinical pharmacology

2018 Volume 84, Issue 12, Page(s) 2836–2848

Abstract: Aim: A Phase 1 study was performed to evaluate safety, pharmacokinetics (PK) and pharmacodynamics (PD) of the selective histamine H: Methods: One hundred healthy subjects were randomized in a placebo-controlled, double-blind study evaluating single- ... ...

Abstract	Aim: A Phase 1 study was performed to evaluate safety, pharmacokinetics (PK) and pharmacodynamics (PD) of the selective histamine H Methods: One hundred healthy subjects were randomized in a placebo-controlled, double-blind study evaluating single-ascending doses (SAD; 100-500 mg) and multiple-ascending doses (MAD; 50-150 mg day Results: SENS-111 was well tolerated with mild to moderate events. No sedation was reported. A maximal tolerated dose was not reached. Dose-proportional increases in concentrations were seen up to 200 mg and more than dose-proportional thereafter, with mean half-life between 24 and 56 h. The caloric test induced mild but measurable vertigo and nystagmus with large intra/inter-individual variation for all parameters. SENS-111 did not significantly impact nystagmus but significantly improved latency of vertigo appearance/disappearance, duration and European Evaluation of Vertigo questionnaire parameters vs. baseline. A two-compartment model with first-order absorption, distribution and elimination best fit the data. PK/PD indirect modelling applied to vertigo duration and latency of appearance indicated maximum activity between 100 and 500 ng ml Conclusions: SENS-111 is a well-tolerated first-in-class H
MeSH term(s)	Adolescent ; Adult ; Azetidines/adverse effects ; Azetidines/pharmacokinetics ; Azetidines/pharmacology ; Caloric Tests ; Double-Blind Method ; Healthy Volunteers ; Histamine Antagonists/adverse effects ; Histamine Antagonists/pharmacokinetics ; Histamine Antagonists/pharmacology ; Humans ; Male ; Middle Aged ; Models, Biological ; Pyrimidines/adverse effects ; Pyrimidines/pharmacokinetics ; Pyrimidines/pharmacology ; Receptors, Histamine H4/antagonists & inhibitors ; Vertigo/drug therapy ; Young Adult
Chemical Substances	Azetidines ; Histamine Antagonists ; Pyrimidines ; Receptors, Histamine H4 ; seliforant
Language	English
Publishing date	2018-10-01
Publishing country	England
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	188974-6
ISSN	1365-2125 ; 0306-5251 ; 0264-3774
ISSN (online)	1365-2125
ISSN	0306-5251 ; 0264-3774
DOI	10.1111/bcp.13744
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Zs.A 1118: Show issues

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Article ; Online: Modulation of hair cell efferents.

Wersinger, Eric / Fuchs, Paul Albert

Hearing research

2010 Volume 279, Issue 1-2, Page(s) 1–12

Abstract: Outer hair cells (OHCs) amplify the sound-evoked motion of the basilar membrane to enhance acoustic sensitivity and frequency selectivity. Medial olivocochlear (MOC) efferents inhibit OHCs to reduce the sound-evoked response of cochlear afferent neurons. ...

Abstract	Outer hair cells (OHCs) amplify the sound-evoked motion of the basilar membrane to enhance acoustic sensitivity and frequency selectivity. Medial olivocochlear (MOC) efferents inhibit OHCs to reduce the sound-evoked response of cochlear afferent neurons. OHC inhibition occurs through the activation of postsynaptic α9α10 nicotinic receptors tightly coupled to calcium-dependent SK2 channels that hyperpolarize the hair cell. MOC neurons are cholinergic but a number of other neurotransmitters and neuromodulators have been proposed to participate in efferent transmission, with emerging evidence for both pre- and postsynaptic effects. Cochlear inhibition in vivo is maximized by repetitive activation of the efferents, reflecting facilitation and summation of transmitter release onto outer hair cells. This review summarizes recent studies on cellular and molecular mechanisms of cholinergic inhibition and the regulation of those molecular components, in particular the involvement of intracellular calcium. Facilitation at the efferent synapse is compared in a variety of animals, as well as other possible mechanisms of modulation of ACh release. These results suggest that short-term plasticity contributes to effective cholinergic inhibition of hair cells.
MeSH term(s)	Animals ; Calcium/metabolism ; Calcium Signaling ; Cochlea/metabolism ; Cochlea/pathology ; Efferent Pathways/metabolism ; Electric Stimulation ; Hair Cells, Auditory/cytology ; Hair Cells, Auditory, Outer/cytology ; Humans ; Ion Channels/metabolism ; Mice ; Mice, Knockout ; Neurotransmitter Agents/metabolism ; Permeability ; Receptors, Nicotinic/metabolism ; Synapses/metabolism ; Synaptic Transmission
Chemical Substances	Ion Channels ; Neurotransmitter Agents ; Receptors, Nicotinic ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2010-12-25
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	282629-x
ISSN	1878-5891 ; 0378-5955
ISSN (online)	1878-5891
ISSN	0378-5955
DOI	10.1016/j.heares.2010.12.018
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Zs.A 1467: Show issues

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Article ; Online: Activation of BK and SK channels by efferent synapses on outer hair cells in high-frequency regions of the rodent cochlea.

Rohmann, Kevin N / Wersinger, Eric / Braude, Jeremy P / Pyott, Sonja J / Fuchs, Paul Albert

The Journal of neuroscience : the official journal of the Society for Neuroscience

2015 Volume 35, Issue 5, Page(s) 1821–1830

Abstract: Cholinergic neurons of the brainstem olivary complex project to and inhibit outer hair cells (OHCs), refining acoustic sensitivity of the mammalian cochlea. In all vertebrate hair cells studied to date, cholinergic inhibition results from the combined ... ...

Abstract	Cholinergic neurons of the brainstem olivary complex project to and inhibit outer hair cells (OHCs), refining acoustic sensitivity of the mammalian cochlea. In all vertebrate hair cells studied to date, cholinergic inhibition results from the combined action of ionotropic acetylcholine receptors and associated calcium-activated potassium channels. Although inhibition was thought to involve exclusively small conductance (SK potassium channels), recent findings have shown that BK channels also contribute to inhibition in basal, high-frequency OHCs after the onset of hearing. Here we show that the waveform of randomly timed IPSCs (evoked by high extracellular potassium) in high-frequency OHCs is altered by blockade of either SK or BK channels, with BK channels supporting faster synaptic waveforms and SK channels supporting slower synaptic waveforms. Consistent with these findings, IPSCs recorded from high-frequency OHCs that express BK channels are briefer than IPSCs recorded from low-frequency (apical) OHCs that do not express BK channels and from immature high-frequency OHCs before the developmental onset of BK channel expression. Likewise, OHCs of BKα(-/-) mice lacking the pore-forming α-subunit of BK channels have longer IPSCs than do the OHCs of BKα(+/+) littermates. Furthermore, serial reconstruction of electron micrographs showed that postsynaptic cisterns of BKα(-/-) OHCs were smaller than those of BKα(+/+) OHCs, and immunofluorescent quantification showed that efferent presynaptic terminals of BKα(-/-) OHCs were smaller than those of BKα(+/+) OHCs. Together, these findings indicate that BK channels contribute to postsynaptic function, and influence the structural maturation of efferent-OHC synapses.
MeSH term(s)	Animals ; Cholinergic Neurons/metabolism ; Cholinergic Neurons/physiology ; Female ; Hair Cells, Auditory, Outer/metabolism ; Hair Cells, Auditory, Outer/physiology ; Inhibitory Postsynaptic Potentials ; Large-Conductance Calcium-Activated Potassium Channels/antagonists & inhibitors ; Large-Conductance Calcium-Activated Potassium Channels/genetics ; Large-Conductance Calcium-Activated Potassium Channels/metabolism ; Male ; Mice ; Neurons, Efferent/metabolism ; Neurons, Efferent/physiology ; Potassium Channel Blockers/pharmacology ; Rats ; Rats, Sprague-Dawley ; Small-Conductance Calcium-Activated Potassium Channels/antagonists & inhibitors ; Small-Conductance Calcium-Activated Potassium Channels/genetics ; Small-Conductance Calcium-Activated Potassium Channels/metabolism ; Synapses/metabolism ; Synapses/physiology
Chemical Substances	Large-Conductance Calcium-Activated Potassium Channels ; Potassium Channel Blockers ; Small-Conductance Calcium-Activated Potassium Channels
Language	English
Publishing date	2015-02-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	604637-x
ISSN	1529-2401 ; 0270-6474
ISSN (online)	1529-2401
ISSN	0270-6474
DOI	10.1523/JNEUROSCI.2790-14.2015
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Zs.A 1668: Show issues

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Article ; Online: Onset of cholinergic efferent synaptic function in sensory hair cells of the rat cochlea.

Roux, Isabelle / Wersinger, Eric / McIntosh, J Michael / Fuchs, Paul A / Glowatzki, Elisabeth

The Journal of neuroscience : the official journal of the Society for Neuroscience

2011 Volume 31, Issue 42, Page(s) 15092–15101

Abstract: In the developing mammalian cochlea, the sensory hair cells receive efferent innervation originating in the superior olivary complex. This input is mediated by α9/α10 nicotinic acetylcholine receptors (nAChRs) and is inhibitory due to the subsequent ... ...

Abstract	In the developing mammalian cochlea, the sensory hair cells receive efferent innervation originating in the superior olivary complex. This input is mediated by α9/α10 nicotinic acetylcholine receptors (nAChRs) and is inhibitory due to the subsequent activation of calcium-dependent SK2 potassium channels. We examined the acquisition of this cholinergic efferent input using whole-cell voltage-clamp recordings from inner hair cells (IHCs) in acutely excised apical turns of the rat cochlea from embryonic day 21 to postnatal day 8 (P8). Responses to 1 mm acetylcholine (ACh) were detected from P0 on in almost every IHC. The ACh-activated current amplitude increased with age and demonstrated the same pharmacology as α9-containing nAChRs. Interestingly, at P0, the ACh response was not coupled to SK2 channels, so that the initial cholinergic response was excitatory and could trigger action potentials in IHCs. Coupling to SK current was detected earliest at P1 in a subset of IHCs and by P3 in every IHC studied. Clustered nAChRs and SK2 channels were found on IHCs from P1 on using Alexa Fluor 488 conjugated α-bungarotoxin and SK2 immunohistochemistry. The number of nAChRs clusters increased with age to 16 per IHC at P8. Cholinergic efferent synaptic currents first appeared in a subset of IHCs at P1 and by P3 in every IHC studied, contemporaneously with ACh-evoked SK currents, suggesting that SK2 channels may be necessary at onset of synaptic function. An analogous pattern of development was observed for the efferent synapses that form later (P6-P8) on outer hair cells in the basal cochlea.
MeSH term(s)	Acetylcholine/pharmacology ; Analysis of Variance ; Animals ; Animals, Newborn ; Apamin/pharmacology ; Biophysics ; Bungarotoxins/metabolism ; Cholinergic Agents/metabolism ; Cochlea/cytology ; Cochlea/embryology ; Cochlea/growth & development ; Electric Stimulation ; Embryo, Mammalian ; Excitatory Postsynaptic Potentials/drug effects ; Excitatory Postsynaptic Potentials/physiology ; Female ; Gene Expression Regulation, Developmental/physiology ; Glycine Agents/pharmacology ; Hair Cells, Auditory/physiology ; Male ; Patch-Clamp Techniques/methods ; Pyridinium Compounds/metabolism ; Quaternary Ammonium Compounds/metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Nicotinic/metabolism ; Small-Conductance Calcium-Activated Potassium Channels/metabolism ; Strychnine/pharmacology ; Synapses/drug effects ; Synapses/physiology ; Time Factors
Chemical Substances	Bungarotoxins ; Cholinergic Agents ; FM 4-64 ; Glycine Agents ; Pyridinium Compounds ; Quaternary Ammonium Compounds ; Receptors, Nicotinic ; Small-Conductance Calcium-Activated Potassium Channels ; Apamin (24345-16-2) ; Strychnine (H9Y79VD43J) ; Acetylcholine (N9YNS0M02X)
Language	English
Publishing date	2011-10-20
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	604637-x
ISSN	1529-2401 ; 0270-6474
ISSN (online)	1529-2401
ISSN	0270-6474
DOI	10.1523/JNEUROSCI.2743-11.2011
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Zs.A 1668: Show issues

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Article ; Online: Symptomatic treatment of vestibular deficits: therapeutic potential of histamine H4 receptors.

Wersinger, Eric / Gaboyard-Niay, Sophie / Travo, Cécile / Soto, Enrique / Baez, Adriana / Vega, Rosario / Brugeaud, Aurore / Chabbert, Christian

Journal of vestibular research : equilibrium & orientation

2013 Volume 23, Issue 3, Page(s) 153–159

Abstract: Vestibular disorders display high prevalence and can severely impact the daily life. However, pharmacological options that would efficiently relieve the vertigo symptoms without side effects are still lacking. In the present review we briefly review the ... ...

Abstract	Vestibular disorders display high prevalence and can severely impact the daily life. However, pharmacological options that would efficiently relieve the vertigo symptoms without side effects are still lacking. In the present review we briefly review the common history of histamine receptor modulation and the pharmacological therapy of vestibular disorders. We also discuss the recent demonstration of Histamine H4 Receptor mRNAs expression in Scarpa's ganglion of mammal and the potential use of specific H4R antagonists as vestibulomodulators. Additional original data confirm the expression of H4R proteins in the rat vestibular primary neurons, the neuromodulatory properties of specific H4R antagonists in vitro (inhibition of vestibular neuron excitability) as well as their efficacy to decrease vestibular deficits induced in different in animal models.
MeSH term(s)	Animals ; Betahistine/therapeutic use ; Histamine Antagonists/therapeutic use ; Histamine H1 Antagonists/therapeutic use ; Neurons, Afferent/drug effects ; Rats ; Receptors, G-Protein-Coupled/drug effects ; Receptors, Histamine/drug effects ; Receptors, Histamine H4 ; Reflex, Vestibulo-Ocular
Chemical Substances	HRH4 protein, human ; Histamine Antagonists ; Histamine H1 Antagonists ; Receptors, G-Protein-Coupled ; Receptors, Histamine ; Receptors, Histamine H4 ; Betahistine (X32KK4201D)
Language	English
Publishing date	2013
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	1051840-x
ISSN	1878-6464 ; 0957-4271
ISSN (online)	1878-6464
ISSN	0957-4271
DOI	10.3233/VES-130493
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Zs.A 3072: Show issues

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Article ; Online: BK channels mediate cholinergic inhibition of high frequency cochlear hair cells.

Wersinger, Eric / McLean, Will J / Fuchs, Paul A / Pyott, Sonja J

PloS one

2010 Volume 5, Issue 11, Page(s) e13836

Abstract: Background: Outer hair cells are the specialized sensory cells that empower the mammalian hearing organ, the cochlea, with its remarkable sensitivity and frequency selectivity. Sound-evoked receptor potentials in outer hair cells are shaped by both ... ...

Abstract	Background: Outer hair cells are the specialized sensory cells that empower the mammalian hearing organ, the cochlea, with its remarkable sensitivity and frequency selectivity. Sound-evoked receptor potentials in outer hair cells are shaped by both voltage-gated K(+) channels that control the membrane potential and also ligand-gated K(+) channels involved in the cholinergic efferent modulation of the membrane potential. The objectives of this study were to investigate the tonotopic contribution of BK channels to voltage- and ligand-gated currents in mature outer hair cells from the rat cochlea. Methodology/principal: Findings In this work we used patch clamp electrophysiology and immunofluorescence in tonotopically defined segments of the rat cochlea to determine the contribution of BK channels to voltage- and ligand-gated currents in outer hair cells. Although voltage and ligand-gated currents have been investigated previously in hair cells from the rat cochlea, little is known about their tonotopic distribution or potential contribution to efferent inhibition. We found that apical (low frequency) outer hair cells had no BK channel immunoreactivity and little or no BK current. In marked contrast, basal (high frequency) outer hair cells had abundant BK channel immunoreactivity and BK currents contributed significantly to both voltage-gated and ACh-evoked K(+) currents. Conclusions/significance: Our findings suggest that basal (high frequency) outer hair cells may employ an alternative mechanism of efferent inhibition mediated by BK channels instead of SK2 channels. Thus, efferent synapses may use different mechanisms of action both developmentally and tonotopically to support high frequency audition. High frequency audition has required various functional specializations of the mammalian cochlea, and as shown in our work, may include the utilization of BK channels at efferent synapses. This mechanism of efferent inhibition may be related to the unique acetylcholine receptors that have evolved in mammalian hair cells compared to those of other vertebrates.
MeSH term(s)	Acetylcholine/pharmacology ; Animals ; Apamin/pharmacology ; Charybdotoxin/pharmacology ; Cholinergic Agents/pharmacology ; Cochlea/cytology ; Hair Cells, Auditory/physiology ; Hair Cells, Auditory, Outer/physiology ; Immunohistochemistry ; Large-Conductance Calcium-Activated Potassium Channels/genetics ; Large-Conductance Calcium-Activated Potassium Channels/metabolism ; Large-Conductance Calcium-Activated Potassium Channels/physiology ; Membrane Potentials/drug effects ; Mice ; Mice, Knockout ; Neurons, Efferent/drug effects ; Neurons, Efferent/physiology ; Patch-Clamp Techniques ; Peptides/pharmacology ; Rats ; Rats, Sprague-Dawley ; Synapses/drug effects ; Synapses/physiology
Chemical Substances	Cholinergic Agents ; Large-Conductance Calcium-Activated Potassium Channels ; Peptides ; Charybdotoxin (115422-61-2) ; Apamin (24345-16-2) ; iberiotoxin (773HER9B6T) ; Acetylcholine (N9YNS0M02X)
Language	English
Publishing date	2010-11-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0013836
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Article ; Online: Reevaluation of dystrophin localization in the mouse retina.

Wersinger, Eric / Bordais, Agnès / Schwab, Yannick / Sene, Abdoulaye / Bénard, Romain / Alunni, Violaine / Sahel, José-Alain / Rendon, Alvaro / Roux, Michel J

Investigative ophthalmology & visual science

2011 Volume 52, Issue 11, Page(s) 7901–7908

Abstract: PURPOSE. The roles of dystrophins in retinal physiology remain elusive. The lack of proper clustering of the potassium channel Kir4.1 and of the aquaporin AQP4 was proposed to be the basis of the ERG abnormality observed in many Duchenne muscular ... ...

Abstract	PURPOSE. The roles of dystrophins in retinal physiology remain elusive. The lack of proper clustering of the potassium channel Kir4.1 and of the aquaporin AQP4 was proposed to be the basis of the ERG abnormality observed in many Duchenne muscular dystrophy (DMD) patients. However, the electroretinogram of Dp71-null mice, in which this clustering is disrupted, shows only a moderate reduction of the b-wave with no change in the implicit times. Additionally, the deficit in color discrimination found in DMD patients is hard to explain through the known expression of DMD gene products. The authors thus decided to reexamine their distribution in the mouse retina. METHODS. Messenger RNA distribution was assessed by PCR coupled to laser microdissection of the outer and inner nuclear layers and by in situ hybridization for Dp427. Mouse retinas were double labeled for dystrophins versus presynaptic and postsynaptic proteins or antibodies specific for Dp427 or Dp427+Dp260. RESULTS. Messengers for Dp427, Dp260, and Dp140 were present in the inner nuclear layer. Dp427 mRNA was further detected in bipolar cells and in some amacrine cells by in situ hybridization. Comparative labeling in wild-type and mdx(5Cv) retinas (lacking Dp427) indicated a differential distribution of Dp427 and Dp260 between rod and cone terminals. CONCLUSIONS. In addition to their localization in photoreceptor terminals, Dp427, Dp260, and Dp140 are expressed in inner nuclear layer neurons, notably in bipolar cells for Dp427. Dp427 was proportionally more expressed in cone- than in rod-associated synapses compared with Dp260.
MeSH term(s)	Animals ; DNA Primers/chemistry ; Dystrophin/genetics ; Gene Expression Regulation/physiology ; Immunohistochemistry ; In Situ Hybridization ; Laser Capture Microdissection ; Mice ; Mice, Inbred C57BL ; Photoreceptor Cells, Vertebrate/metabolism ; RNA, Messenger/metabolism ; Real-Time Polymerase Chain Reaction ; Retina/metabolism ; Retinal Neurons/metabolism ; Synapses/metabolism
Chemical Substances	DNA Primers ; Dystrophin ; RNA, Messenger ; apo-dystrophin 1
Language	English
Publishing date	2011-10-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	391794-0
ISSN	1552-5783 ; 0146-0404
ISSN (online)	1552-5783
ISSN	0146-0404
DOI	10.1167/iovs.11-7519
Database	MEDical Literature Analysis and Retrieval System OnLINE

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