Differential membrane redistribution of P2X receptor isoforms in response to osmotic and hyperglycemic stress in the rat lens

P2X_{1, 2, 3, 4, 6 and 7} are all expressed in a differentiation-dependent manner in the rat lens. However, in the lens outer cortex the subcellular distribution of all P2X isoforms is predominantly associated with a pool of receptors located in cytoplasmic vesicles. Here we investigate whether osmotic and hyperglycemic stress can alter the subcellular distribution of this cytoplasmic pool of P2X receptors. We show that in a discrete zone of the deeper outer cortex an isoform and stimulus-specific shift in the subcellular distribution of P2X receptors occurs from the cytoplasm to defined membrane domains. In response to hypertonic stress P2X₁ and P2X₄ isoforms became more closely associated with the broad sides of fiber cells, while under hypotonic conditions P2X₄ and P2X₆ isoforms associate with the narrow side membranes. No such changes in subcellular distribution were observed for P2X_{2,3 and 7} isoforms. Lens cultured in 50 mM glucose exhibited cell swelling in this zone but only P2X₄ associated with narrow side membranes. Our results indicate P2X receptors can be differentially recruited to specific membrane domains of lens fiber cells by osmotic and hyperglycemic stress. Furthermore they suggest the involvement of specific P2X isoforms in the regulation of fiber cell volume and the initiation of diabetic cataract.