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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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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 (pH i ). 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 Ca 2+ elevation mediated by stimulating reverse mode operation of Na + /Ca 2+ exchange (NCX rev ). Taken together, our study shows that NHE-1 protein is abundantly expressed in microglial lamellipodia and maintains alkaline pH i in response to BK stimulation. In addition, NHE-1 and NCX rev play a concerted role in BK-induced microglial migration via Na + and Ca 2+ signaling. © 2013 Shi et al.


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Item Type: Article
Status: Published
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: 09 Apr 2019 15:55


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