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Sodium channels enable fast electrical signaling and regulate phagocytosis in the retinal pigment epithelium

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Sodium channels enable fast electrical signaling and regulate phagocytosis in the retinal pigment epithelium. / Johansson, Julia K.; Karema-Jokinen, Viivi I.; Hakanen, Satu; Jylhä, Antti; Uusitalo, Hannu; Vihinen-Ranta, Maija; Skottman, Heli; Ihalainen, Teemu O.; Nymark, Soile.

In: BMC BIOLOGY, Vol. 17, No. 1, 63, 15.08.2019.

Research output: Contribution to journalArticleScientificpeer-review

Harvard

Johansson, JK, Karema-Jokinen, VI, Hakanen, S, Jylhä, A, Uusitalo, H, Vihinen-Ranta, M, Skottman, H, Ihalainen, TO & Nymark, S 2019, 'Sodium channels enable fast electrical signaling and regulate phagocytosis in the retinal pigment epithelium', BMC BIOLOGY, vol. 17, no. 1, 63. https://doi.org/10.1186/s12915-019-0681-1

APA

Vancouver

Johansson JK, Karema-Jokinen VI, Hakanen S, Jylhä A, Uusitalo H, Vihinen-Ranta M et al. Sodium channels enable fast electrical signaling and regulate phagocytosis in the retinal pigment epithelium. BMC BIOLOGY. 2019 Aug 15;17(1). 63. https://doi.org/10.1186/s12915-019-0681-1

Author

Johansson, Julia K. ; Karema-Jokinen, Viivi I. ; Hakanen, Satu ; Jylhä, Antti ; Uusitalo, Hannu ; Vihinen-Ranta, Maija ; Skottman, Heli ; Ihalainen, Teemu O. ; Nymark, Soile. / Sodium channels enable fast electrical signaling and regulate phagocytosis in the retinal pigment epithelium. In: BMC BIOLOGY. 2019 ; Vol. 17, No. 1.

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@article{b5467b174eb44351994b18413ca674a1,
title = "Sodium channels enable fast electrical signaling and regulate phagocytosis in the retinal pigment epithelium",
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 = "Ion channels, Na, Patch clamp, Phagocytosis, Photoreceptors, Retina, RPE",
author = "Johansson, {Julia K.} and Karema-Jokinen, {Viivi I.} and Satu Hakanen and Antti Jylh{\"a} and Hannu Uusitalo and Maija Vihinen-Ranta and Heli Skottman and Ihalainen, {Teemu O.} and Soile Nymark",
year = "2019",
month = "8",
day = "15",
doi = "10.1186/s12915-019-0681-1",
language = "English",
volume = "17",
journal = "BMC BIOLOGY",
issn = "1741-7007",
number = "1",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Sodium channels enable fast electrical signaling and regulate phagocytosis in the retinal pigment epithelium

AU - Johansson, Julia K.

AU - Karema-Jokinen, Viivi I.

AU - Hakanen, Satu

AU - Jylhä, Antti

AU - Uusitalo, Hannu

AU - Vihinen-Ranta, Maija

AU - Skottman, Heli

AU - Ihalainen, Teemu O.

AU - Nymark, Soile

PY - 2019/8/15

Y1 - 2019/8/15

N2 - 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.

AB - 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.

KW - Ion channels

KW - Na

KW - Patch clamp

KW - Phagocytosis

KW - Photoreceptors

KW - Retina

KW - RPE

U2 - 10.1186/s12915-019-0681-1

DO - 10.1186/s12915-019-0681-1

M3 - Article

VL - 17

JO - BMC BIOLOGY

JF - BMC BIOLOGY

SN - 1741-7007

IS - 1

M1 - 63

ER -