PT  - JOURNAL ARTICLE
AU  - Julia K. Johansson
AU  - Teemu O. Ihalainen
AU  - Heli Skottman
AU  - Soile Nymark
TI  - Fast voltage sensitivity in retinal pigment epithelium: sodium channels and their novel role in phagocytosis
AID  - 10.1101/223719
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 223719
4099  - http://biorxiv.org/content/early/2017/11/22/223719.short
4100  - http://biorxiv.org/content/early/2017/11/22/223719.full
AB  - Despite the discoveries of voltage-gated sodium channels (Nav) from a number of non-excitable cell types, the presence of Nav-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 Nav1.4-Nav1.6 and Nav1.8 channels in human embryonic stem cell derived and mouse RPE. Importantly, we show that Navs are involved in photoreceptor outer segment phagocytosis: blocking their activity significantly reduces the efficiency of this process. Consistent with this role, Nav1.8 co-localizes with the endosomal marker Rab7 and, during phagocytosis, with opsin. Nav1.4 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 Navs give the capacity of fast electrical signaling to RPE and that Navs play a novel role in photoreceptor outer segment phagocytosis.