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Peter R. MacLeish, Xiaoming Chen, Tiandong Leng, Mian Xie, Zhigang Xiong; The Expression of Acid-Sensitive Current by Solitary Salamander and Monkey Müller Cells. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1997.
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Müller cells perform multiple functions in maintaining the health of the retina and might be targets of chronic disorders given their intimate contact with all classes of retinal neurons and blood vessels. Here, we investigated whether or not Müller cells were able to respond to low pH since this condition accompanies a variety of retinal disorders. In other systems, neurons and glial cells express Acid-Sensing Ion Channels (ASICs) whose activation by low tissue pH seems to contribute to the pathophysiology of certain disorders.
Müller cells were isolated from the salamander (A. tigrinum) or rhesus monkey (Macaca mulatta) retina following treatment with 7u/ml of papain and trituration. Retinal cells were plated on coverslips coated with the antibody, Sal-1, for salamander or 9B5 for monkey. Membrane current was measured under voltage clamp conditions using the whole cell configuration. Electrodes contained CsF or KCl at pH 7.3. Extracellular pH was changed by fast perfusion of buffered solutions at pH 7.4, pH 6.0, or pH 5.0.
For 40 salamander Müller cells, about 40% responded to pH changes from 7.4 to 6.0 (or 5.0) by a clear increase in inward current. All 5 monkey cells responded with inward current. The amplitude of the induced current and the overall time course were variable but resembled those of currents induced by activation of acid-sensing ion channels (ASICs) in other systems. The range of amplitudes of induced current was between 10 and several hundred pA. In 2 salamander cells where a complete current-voltage relationship was constructed, a reversal potential approaching +60 mV was observed, suggesting the activation of a Na+-selective channel. Interestingly, the currents in salamander Müller cells appear to be resistant to amiloride, a commonly used non-specific blocker for ASICs. In contrast, ganglion cells in the same dish had acid-sensitive inward currents that were blocked by amiloride. The currents in monkey Müller cells were sensitive to amiloride and Psalmotoxin 1 (PcTx1), a specific inhibitor of ASIC-1.
Müller cells from salamander and monkey express acid-sensitive currents that were observed when the extracellular pH was changed from 7.0 to 6.0 or to 5.0. Work in other laboratories has reported the presence of acid-sensitive currents on retinal ganglion cells so our finding indicates that other retinal cells express acid-sensitive currents. Our results indicate that monkey Müller cells express acid-sensing channels with properties of ASICs seen in other systems while salamander Müller cells express channels with distinct pharmacological properties. The molecular basis for this difference and the functional significance are of interest for future studies.
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