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Stimulation of Na<sup>+</sup>/H<sup>+</sup> Exchanger Isoform 1 Promotes Microglial Migration

Shi, Y and Yuan, H and Kim, D and Chanana, V and Baba, A and Matsuda, T and Cengiz, P and Ferrazzano, P and Sun, D (2013) Stimulation of Na<sup>+</sup>/H<sup>+</sup> Exchanger Isoform 1 Promotes Microglial Migration. PLoS ONE, 8 (8).

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Abstract

Regulation of microglial migration is not well understood. In this study, we proposed that Na+/H+ exchanger isoform 1 (NHE-1) is important in microglial migration. NHE-1 protein was co-localized with cytoskeletal protein ezrin in lamellipodia of microglia and maintained its more alkaline intracellular pH (pHi). Chemoattractant bradykinin (BK) stimulated microglial migration by increasing lamellipodial area and protrusion rate, but reducing lamellipodial persistence time. Interestingly, blocking NHE-1 activity with its potent inhibitor HOE 642 not only acidified microglia, abolished the BK-triggered dynamic changes of lamellipodia, but also reduced microglial motility and microchemotaxis in response to BK. In addition, NHE-1 activation resulted in intracellular Na+ loading as well as intracellular Ca2+ elevation mediated by stimulating reverse mode operation of Na+/Ca2+ exchange (NCXrev). Taken together, our study shows that NHE-1 protein is abundantly expressed in microglial lamellipodia and maintains alkaline pHi in response to BK stimulation. In addition, NHE-1 and NCXrev play a concerted role in BK-induced microglial migration via Na+ and Ca2+ signaling. © 2013 Shi et al.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Shi, Yy.shi@pitt.eduYES110000-0001-7502-9201
Yuan, H
Kim, Ddok22@pitt.eduDOK22
Chanana, V
Baba, A
Matsuda, T
Cengiz, P
Ferrazzano, P
Sun, Ddds30@pitt.eduDDS30
Date: 21 August 2013
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 8
Number: 8
DOI or Unique Handle: 10.1371/journal.pone.0074201
Schools and Programs: School of Medicine > Neurology
Refereed: Yes
Date Deposited: 09 Oct 2013 16:25
Last Modified: 03 Dec 2019 16:55
URI: http://d-scholarship.pitt.edu/id/eprint/19798

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