title: Stimulation of Na(+)/H(+) exchanger isoform 1 promotes microglial migration.
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 Ca(2+) elevation mediated by stimulating reverse mode operation of Na(+)/Ca(2+) 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 Ca(2+) signaling.
authors.affiliation: Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Yejie
authors.initials: Y
authors.lastname: Shi
authors.forename: Hui
authors.initials: H
authors.lastname: Yuan
authors.forename: Dong
authors.initials: D
authors.lastname: Kim
authors.forename: Vishal
authors.initials: V
authors.lastname: Chanana
authors.forename: Akemichi
authors.initials: A
authors.lastname: Baba
authors.forename: Toshio
authors.initials: T
authors.lastname: Matsuda
authors.forename: Pelin
authors.initials: P
authors.lastname: Cengiz
authors.forename: Peter
authors.initials: P
authors.lastname: Ferrazzano
authors.forename: Dandan
authors.initials: D
authors.lastname: Sun
mesh_terms: D000818:Animals; D001483:Base Sequence; D020013:Calcium Signaling; D027682:Cation Transport Proteins / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D002633:Chemotaxis; D006863:Hydrogen-Ion Concentration; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000502:physiology*; D020033:Protein Isoforms / Q000502:physiology*; D034622:RNA Interference; D012964:Sodium / Q000378:metabolism; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics / Q000502:physiology*
chemical_list: D027682:Cation Transport Proteins; D020033:Protein Isoforms; C490997:Slc9a1 protein, mouse; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers; D012964:Sodium