Abstract
P2X7Rs are distributed throughout all layers of the retina, and thus, their localisation on various cell types puts into question their specific site(s) of action. Using a dark-adapted, ex vivo mouse retinal whole mount preparation, the present study aimed to characterise the effect of P2X7R activation on light-evoked, excitatory RGC ON-field excitatory post-synaptic potentials (fEPSPs) and on outer retinal electroretinogram (ERG) responses under comparable conditions. The pharmacologically isolated NMDA receptor-mediated RGC ON-fEPSP was reduced in the presence of BzATP, an effect which was significantly attenuated by A438079 and other selective P2X7R antagonists A804598 or AF27139. In physiological Krebs medium, BzATP induced a significant potentiation of the ERG a-wave, with a concomitant reduction in the b-wave and the power of the oscillatory potentials. Conversely, in the pharmacologically modified Mg2+-free perfusate, BzATP reduced both the a-wave and b-wave. The effects of BzATP on the ERG components were suppressed by A438079. A role for P2X7R function in visual processing in both the inner and outer retina under physiological conditions remains controversial. The ON-fEPSP was significantly reduced in the presence of A804598 but not by A438079 or AF27139. Furthermore, A438079 did not have any effect on the ERG components in physiological Krebs but potentiated and reduced the a-wave and b-wave, respectively, when applied to the pharmacologically modified medium. Therefore, activation of P2X7Rs affects the function in the retinal ON pathway. The presence of a high concentration of extracellular ATP would most likely contribute to the modulation of visual transmission in the retina in the pathophysiological microenvironment.
Highlights
The P2X7 receptor (P2X7R) is the most diverse receptor subtype of the P2X family in both structure and function [1]
The present study has demonstrated that neuronal function in both the outer and inner retina of the mouse under darkadapted conditions is considerably altered by P2X7R activation
P2X7R modulation of visual responses appears to occur through independent mechanisms, at different levels of the rod pathway
Summary
The P2X7 receptor (P2X7R) is the most diverse receptor subtype of the P2X family in both structure and function [1]. ATP-gated P2X7Rs have been detected in neurons and glia, in both inner and outer synapse-rich and nuclear layers of the retina. They are functionally expressed by retinal ganglion cells [2,3,4,5,6,7,8,9,10] and Müller glial cells [11], and their presence on amacrine, horizontal [7, 12, 13] and microglial cells [4, 7] has been suggested. Repeated or prolonged agonist application gives rise to a sustained current, which could lead to cell death, Purinergic Signalling (2016) 12:611–625 assumed to be associated with the opening of a large pore that is permeable to molecules of high molecular weight (
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