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NSAIDs modulate GABA-activated currents via Ca2+-activated Cl‑ channels in rat dorsal root ganglion neurons

  • Authors:
    • Lei Zhao
    • Li Li
    • Ke‑Tao Ma
    • Yang Wang
    • Jing Li
    • Wen‑Yan Shi
    • He Zhu
    • Zhong‑Shuang Zhang
    • Jun‑Qiang Si
  • View Affiliations / Copyright

    Affiliations: Department of Physiology, Shihezi University Medical College, Shihezi, Xinjiang 832002, P.R. China
    Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1755-1761
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    Published online on: March 15, 2016
       https://doi.org/10.3892/etm.2016.3158
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Abstract

The ability of non-steroidal anti-inflammatory drugs (NSAIDs) to modulate γ-aminobutyrate (GABA)-activated currents via Ca2+-activated Cl‑ channels in rat dorsal root ganglion neurons (DRG), was examined in the present study. During the preparation of DRG neurons harvested from Sprague‑Dawley rats, the whole‑cell recording technique was used to record the effect of NSAIDs on GABA‑activated inward currents, and the expression levels of the TMEM16A and TMEM16B subunits were revealed. In the event that DRG neurons were pre‑incubated for 20 sec with niflumic acid (NFA) and 5‑nitro‑2‑(3‑phenylpropylamino) benzoic acid (NPPB) prior to the administration of GABA, the GABA‑induced inward currents were diminished markedly in the majority of neurons examined (96.3%). The inward currents induced by 100 µmol/l GABA were attenuated by (0±0.09%; neurons = 4), (5.32±3.51%; neurons = 6), (21.3±4.00%; neurons = 5), (33.8±5.20%; neurons = 17), (52.2±5.10%; neurons = 4) and (61.1±4.12%; neurons = 12) by 0.1, 1, 3, 10, 30 and 100 µmol/l NFA, respectively. The inward currents induced by 100 µmol/l GABA were attenuated by (13.8±6%; neurons = 6), (23.2±14.7%; neurons = 6) and (29.7±9.1%; neurons = 9) by 3, 10 and 30 µmol/l NPPB, respectively. NFA and NPPB dose‑dependently inhibited GABA‑activated currents with half maximal inhibitory concentration (IC50) values of 6.7 and 11 µmol/l, respectively. The inhibitory effect of 100 µmol/l NFA on the GABA‑evoked inward current were also strongly inhibited by nitrendipine (NTDP; an L‑type calcium channel blocker), 1,2‑bis(2‑aminophenoxy)ethane‑N,N,N',N'‑tetraacetic acid tetrakis (a highly selective calcium chelating reagent), caffeine (a widely available Ca2+ consuming drug) and calcium‑free extracellular fluid, in a concentration‑dependent manner. Immunofluorescent staining indicated that TMEM16A and TMEM16B expression was widely distributed in DRG neurons. The results suggest that NSAIDs may be able to regulate Ca2+‑activated chloride channels to reduce GABAa receptor‑mediated inward currents in DRGs.
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Copy and paste a formatted citation
Spandidos Publications style
Zhao L, Li L, Ma KT, Wang Y, Li J, Shi WY, Zhu H, Zhang ZS and Si JQ: NSAIDs modulate GABA-activated currents via Ca2+-activated Cl‑ channels in rat dorsal root ganglion neurons. Exp Ther Med 11: 1755-1761, 2016.
APA
Zhao, L., Li, L., Ma, K., Wang, Y., Li, J., Shi, W. ... Si, J. (2016). NSAIDs modulate GABA-activated currents via Ca2+-activated Cl‑ channels in rat dorsal root ganglion neurons. Experimental and Therapeutic Medicine, 11, 1755-1761. https://doi.org/10.3892/etm.2016.3158
MLA
Zhao, L., Li, L., Ma, K., Wang, Y., Li, J., Shi, W., Zhu, H., Zhang, Z., Si, J."NSAIDs modulate GABA-activated currents via Ca2+-activated Cl‑ channels in rat dorsal root ganglion neurons". Experimental and Therapeutic Medicine 11.5 (2016): 1755-1761.
Chicago
Zhao, L., Li, L., Ma, K., Wang, Y., Li, J., Shi, W., Zhu, H., Zhang, Z., Si, J."NSAIDs modulate GABA-activated currents via Ca2+-activated Cl‑ channels in rat dorsal root ganglion neurons". Experimental and Therapeutic Medicine 11, no. 5 (2016): 1755-1761. https://doi.org/10.3892/etm.2016.3158
Copy and paste a formatted citation
x
Spandidos Publications style
Zhao L, Li L, Ma KT, Wang Y, Li J, Shi WY, Zhu H, Zhang ZS and Si JQ: NSAIDs modulate GABA-activated currents via Ca2+-activated Cl‑ channels in rat dorsal root ganglion neurons. Exp Ther Med 11: 1755-1761, 2016.
APA
Zhao, L., Li, L., Ma, K., Wang, Y., Li, J., Shi, W. ... Si, J. (2016). NSAIDs modulate GABA-activated currents via Ca2+-activated Cl‑ channels in rat dorsal root ganglion neurons. Experimental and Therapeutic Medicine, 11, 1755-1761. https://doi.org/10.3892/etm.2016.3158
MLA
Zhao, L., Li, L., Ma, K., Wang, Y., Li, J., Shi, W., Zhu, H., Zhang, Z., Si, J."NSAIDs modulate GABA-activated currents via Ca2+-activated Cl‑ channels in rat dorsal root ganglion neurons". Experimental and Therapeutic Medicine 11.5 (2016): 1755-1761.
Chicago
Zhao, L., Li, L., Ma, K., Wang, Y., Li, J., Shi, W., Zhu, H., Zhang, Z., Si, J."NSAIDs modulate GABA-activated currents via Ca2+-activated Cl‑ channels in rat dorsal root ganglion neurons". Experimental and Therapeutic Medicine 11, no. 5 (2016): 1755-1761. https://doi.org/10.3892/etm.2016.3158
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