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Sun-Sook Paik, Myung-Hoon Chun, In-Beom Kim; Dual Effect of Niflumic acid on Ca2+-activated Chloride Currents (I Cl(Ca)) in Mouse Retinal Rod-bipolar Cells. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4316.
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We previously have identified Ca2+-activated chloride currents (ICl(Ca)) in the mouse retinal neurons and characterize it by using anatomical and electrophysiological techniques. In the pesent study, we examined dual effects of niflumic acid (NFA), a Cl- channel blocker, on ICl(Ca) in mouse retinal rod-bipolar cells.
Retinal dissociated bipolar cells were prepared from the C57BL/6 mouse. Membrane currents were recorded in the whole-cell recording configuration.
In our previous, ICl(Ca) was identified as a Ca2+-activated tail current following inward Ca2+current in mouse rod-bipolar cells. NFA suppressed ) seletively ICl(Ca in lower concentration (≈100 µM). On the contrary, we found in this study that higher concentration of NFA(≥1mM) enhanced ICa and ICl(Ca) as well. However, this promotive actions of NFA not only decreased when intracellular Ca2+ was strongly chelated with Bapta but also depleting the SR with the combination of caffeine and cyclopiazonic acid inhibited the increase in ICl(Ca) by NFA, indicating that the release of Ca2+ from an intracellular store may be responsible for the observed effect. NFA appeared to increase inward current but blocked outward current, suggesting that the effect of NFA is closely related in current flow. Inclusion of NFA in the pipette solution had no effect on ICl(Ca). In order to examine whether this dual effect could be generalized into all Cl- channel blockers, several Cl- channel blockers were applied. DCDPC (100µM) produced similar effects to NFA but 1 mM DIDS produced inhibition of ICl(Ca) and there was no increase in current on wash out of DIDS.
These results suggest that NFA enhance and block ICl(Ca) in mouse retinal bipolar cells by binding to an external site, probably close to the mouth of the chloride channel. The dual effect of NFA is likely due to Ca2+ release from an intracellular store, most probably the SR in dose-dependent manner.
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