Intermediate-conductance calcium-activated potassium channel KCa3.1 and chloride channel modulate chemokine ligand (CCL19/CCL21)-induced migration of dendritic cells

Zhifei Shao, Rohit Gaurav, Devendra K. Agrawal

    Research output: Contribution to journalArticlepeer-review

    8 Scopus citations

    Abstract

    The role of ion channels is largely unknown in chemokine-induced migration in nonexcitable cells such as dendritic cells (DCs). Here, we examined the role of intermediate-conductance calcium-activated potassium channel (KCa3.1) and chloride channel (CLC3) in lymphatic chemokine-induced migration of DCs. The amplitude and kinetics of chemokine ligand (CCL19/CCL21)-induced Ca2+ influx were associated with chemokine receptor 7 expression levels, extracellular-free Ca2+ and Cl-, and independent of extracellular K+. Chemokines (CCL19 and CCL21) and KCa3.1 activator (1-ethyl-1,3-dihydro-2H-benzimidazol-2-one) induced plasma membrane hyperpolarization and K+ efflux, which was blocked by 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole, suggesting that KCa3.1 carried larger conductance than the inward calcium release-activated calcium channel. Blockade of KCa3.1, low Cl- in the medium, and low dose of 4,4′-diisothiocyano-2,2′-stilbenedisulfonic acid (DIDS) impaired CCL19/CCL21-induced Ca2+ influx, cell volume change, and DC migration. High doses of DIDS completely blocked DC migration possibly by significantly disrupting mitochondrial membrane potential. In conclusion, KCa3.1 and CLC3 are critical in human DC migration by synergistically regulating membrane potential, chemokine-induced Ca2+ influx, and cell volume.

    Original languageEnglish
    Pages (from-to)89-102
    Number of pages14
    JournalTranslational Research
    Volume166
    Issue number1
    DOIs
    StatePublished - Jul 1 2015

    All Science Journal Classification (ASJC) codes

    • Medicine(all)
    • Biochemistry, medical
    • Public Health, Environmental and Occupational Health

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