A1 Journal article (refereed)
Sodium channels enable fast electrical signaling and regulate phagocytosis in the retinal pigment epithelium (2019)


Johansson, Julia K.; Karema-Jokinen, Viivi I.; Hakanen, Satu; Jylhä, Antti; Uusitalo, Hannu; Vihinen-Ranta, Maija; Skottman, Heli; Ihalainen, Teemu O.; Nymark, Soile (2019). Sodium channels enable fast electrical signaling and regulate phagocytosis in the retinal pigment epithelium. BMC Biology, 17, 63. DOI: 10.1186/s12915-019-0681-1


JYU authors or editors


Publication details

All authors or editors: Johansson, Julia K.; Karema-Jokinen, Viivi I.; Hakanen, Satu; Jylhä, Antti; Uusitalo, Hannu; Vihinen-Ranta, Maija; Skottman, Heli; Ihalainen, Teemu O.; Nymark, Soile

Journal or series: BMC Biology

eISSN: 1741-7007

Publication year: 2019

Volume: 17

Article number: 63

Publisher: BioMed Central Ltd.

Publication country: United Kingdom

Publication language: English

DOI: https://doi.org/10.1186/s12915-019-0681-1

Open Access: Publication published in an open access channel

Publication is parallel published (JYX): https://jyx.jyu.fi/handle/123456789/65292


Abstract

Background
Voltage-gated sodium (Nav) channels have traditionally been considered a trademark of excitable cells. However, recent studies have shown the presence of Nav channels in several non-excitable cells, such as astrocytes and macrophages, demonstrating that the roles of these channels are more diverse than was previously thought. Despite the earlier discoveries, the presence of Nav channel-mediated currents in the cells of retinal pigment epithelium (RPE) has been dismissed as a cell culture artifact. We challenge this notion by investigating the presence and possible role of Nav channels in RPE both ex vivo and in vitro.

Results
Our work demonstrates that several subtypes of Nav channels are found in human embryonic stem cell (hESC)-derived and mouse RPE, most prominently subtypes Nav1.4, Nav1.6, and Nav1.8. Whole cell patch clamp recordings from the hESC-derived RPE monolayers showed that the current was inhibited by TTX and QX-314 and was sensitive to the selective blockers of the main Nav subtypes. Importantly, we show that the Nav channels are involved in photoreceptor outer segment phagocytosis since blocking their activity significantly reduces the efficiency of particle internalization. Consistent with this role, our electron microscopy results and immunocytochemical analysis show that Nav1.4 and Nav1.8 accumulate on phagosomes and that pharmacological inhibition of Nav channels as well as silencing the expression of Nav1.4 with shRNA impairs the phagocytosis process.

Conclusions
Taken together, our study shows that Nav channels are present in RPE, giving this tissue the capacity of fast electrical signaling. The channels are critical for the physiology of RPE with an important role in photoreceptor outer segment phagocytosis.


Keywords: proteins; cell signaling; phagocytosis; sensory receptor cells; retina

Free keywords: RPE; ion channels; Nav; patch clamp; phagocytosis; retina; photoreceptors


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Ministry reporting: Yes

Reporting Year: 2019

JUFO rating: 2


Last updated on 2020-18-08 at 13:07