Dimethyl sulfoxide (DMSO) blocks GABA-induced current in rat dorsal root ganglion neurons

Nakahiro, Masanobu; Arakawa, Osamu; Narahashi, Toshio; Ukai, Shigeo; Kato, Yoshiya; Nishinuma, Keiji; Nishimura, Tsuyoshi

doi:10.1016/0304-3940(92)90459-k

Cited by 48 publications

(26 citation statements)

References 9 publications

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“…Isolated in vitro studies on rat retinal cells suggest that DMSO-induced membrane permeability changes lead to depolarization of BCs, resulting in an increased or decreased b-wave signal depending on concentration [44]. A potentiation of glutamatergic neurotransmission by DMSO has also been reported [45] as well as suppression of GABAergic inhibitory currents at very low concentrations (\0.6%) [46]. Although such changes at a cellular level should act to increase rather than decrease ERG waveforms from post-receptoral neurons, opposing effects of low and high concentrations of DMSO have been reported [19,47].…”

Section: Discussionmentioning

confidence: 97%

Dimethyl sulphoxide dose–response on rat retinal function

2009

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The aim of the study is to determine whether dimethyl sulphoxide (DMSO), a common laboratory solvent, impacts retinal function. Long Evans rats (n = 17) were intravitreally injected with five different doses of DMSO representative of those reported in the literature and spanning over 3 log units of vitreal concentration (0.01-8%). Retinal function was evaluated 1 h after injection using electroretinograms, and the waveform was decomposed into outer (photoreceptor), middle (ON-bipolar cell) and inner retinal (amacrine and ganglion cell) components. DMSO induces a dose-dependent decrease in retinal function for concentrations of 0.6% or more which is retinal layer specific. The photoreceptors of the outer retina returned normal responses at all doses (P > 0.05), whereas the mid-retinal bipolar cell response showed dose-dependent losses ranging from 21 +/- 1 to 82 +/- 1% (0.6-8% DMSO; P < 0.05). In a similar dose-dependent fashion, the inner retinal response was also affected by DMSO (0.6-8%: 23 +/- 12 to 98 +/- 3% loss, P < 0.05). A single dose of DMSO < or =0.1% (2.96 x 10(-5) microM) may be safely used to dilute compounds injected into the vitreous of a rat eye. Higher doses produce short-term (at least 24 h) retinal dysfunction.

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Section: Discussionmentioning

confidence: 97%

Dimethyl sulphoxide dose–response on rat retinal function

2009

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“…All experiments were performed at room temperature (&18-23°C). In cases where drugs were applied from a DMSO-containing stock solution, DMSO concentration was less than 0.1% to avoid any influences on the patch-clamp recordings (Nakahiro et al 1992). Channel behavior was characterized based on responses to voltage protocols and perfusion of appropriate compounds and solutions (Bruggemann et al 2006;Milligan et al 2009).…”

Section: Planar Patch-clamp Recordingmentioning

confidence: 99%

Calcium regulation by thermo- and osmosensing transient receptor potential vanilloid channels (TRPVs) in human conjunctival epithelial cells

Mergler

Garreis

Sahlmüller

et al. 2012

Histochem Cell Biol

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Transient receptor potential vanilloid (TRPV) channels respond to polymodal stresses to induce pain, inflammation and tissue fibrosis. In this study, we probed for their functional expression in human conjunctival epithelial (HCjE) cells and ex vivo human conjunctivas. Notably, patients suffering from dry eye syndrome experience the same type of symptomology induced by TRPV channel activation in other ocular tissues. TRPV gene and protein expression were determined by RT-PCR and immunohistochemistry in HCjE cells and human conjunctivas (body donors). The planar patch-clamp technique was used to record nonselective cation channel currents. Ca(2+) transients were monitored in fura-2 loaded cells. Cultivated HCjE cells and human conjunctiva express TRPV1, TRPV2, and TRPV4 mRNA. TRPV1 and TRPV4 localization was identified in human conjunctiva. Whereas the TRPV1 agonist capsaicin (CAP) (5-20 μM) -induced Ca(2+) transients were blocked by capsazepine (CPZ) (10 μM), the TRPV4 activator 4α-PDD (10 μM) -induced Ca(2+) increases were reduced by ruthenium-red (RuR) (20 μM). Different heating (<40°C or >43°C) led to Ca(2+) increases, which were also reduced by RuR. Hypotonic challenges of either 25 or 50% induced Ca(2+) transients and nonselective cation channel currents. In conclusion, conjunctiva express TRPV1, TRPV2, and TRPV4 channels which may provide novel drug targets for dry eye therapeutics. Their usage may have fewer side effects than those currently encountered with less selective drugs.

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“…A stock solution of ganaxolone was made in DMSO and diluted with saline (pH 7.1) before systemic administration. The final concentration of DMSO was 0.1%, a concentration known not to interfere with GABA A -R function (30). Ganaxolone (10 mg͞kg, i.p.)…”

Section: Loss Of Righting Reflex (Lorr) and Tail-clamp͞withdrawal Assaymentioning

confidence: 99%

Attenuated sensitivity to neuroactive steroids in γ-aminobutyrate type A receptor delta subunit knockout mice

Mihalek

Banerjee

Korpi

et al. 1999

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

491

417

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␥-Aminobutyric acid (GABA) type A receptors mediate fast inhibitory synaptic transmission and have been implicated in responses to sedative͞hypnotic agents (including neuroactive steroids), anxiety, and learning and memory. Using gene targeting technology, we generated a strain of mice deficient in the ␦ subunit of the GABA type A receptors. In vivo testing of various behavioral responses revealed a strikingly selective attenuation of responses to neuroactive steroids, but not to other modulatory drugs. Electrophysiological recordings from hippocampal slices revealed a significantly faster miniature inhibitory postsynaptic current decay time in null mice, with no change in miniature inhibitory postsynaptic current amplitude or frequency. Learning and memory assessed with fear conditioning were normal. These results begin to illuminate the novel contributions of the ␦ subunit to GABA pharmacology and sedative͞hypnotic responses and behavior and provide insights into the physiology of neurosteroids.

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Dimethyl sulfoxide (DMSO) blocks GABA-induced current in rat dorsal root ganglion neurons

Cited by 48 publications

References 9 publications

Dimethyl sulphoxide dose–response on rat retinal function

Dimethyl sulphoxide dose–response on rat retinal function

Calcium regulation by thermo- and osmosensing transient receptor potential vanilloid channels (TRPVs) in human conjunctival epithelial cells

Attenuated sensitivity to neuroactive steroids in γ-aminobutyrate type A receptor delta subunit knockout mice

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