Fast voltage sensitivity in retinal pigment epithelium: sodium channels and their novel role in phagocytosis

Abstract

Despite the discoveries of voltage-gated sodium channels (Na _v ) from a number of non-excitable cell types, the presence of Na _v -mediated currents in cells of the retinal pigment epithelium (RPE) has been dismissed as a cell culture artifact. Here, we challenge this notion by demonstrating functional Na _v 1.4-Na _v 1.6 and Na _v 1.8 channels in human embryonic stem cell derived and mouse RPE. Importantly, we show that Na _v s are involved in photoreceptor outer segment phagocytosis: blocking their activity significantly reduces the efficiency of this process. Consistent with this role, Na _v 1.8 co-localizes with the endosomal marker Rab7 and, during phagocytosis, with opsin. Na _v 1.4 localizes strongly to the cell-cell junctions together with the gap junction protein Connexin 43. During phagocytosis, both are localized to the phagosomes with a concurrent decrease in the junctional localization. Our study demonstrates that Na _v s give the capacity of fast electrical signaling to RPE and that Na _v s play a novel role in photoreceptor outer segment phagocytosis.