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Neurochemical Research

, Volume 41, Issue 8, pp 1982–1992 | Cite as

CNTF-Treated Astrocyte Conditioned Medium Enhances Large-Conductance Calcium-Activated Potassium Channel Activity in Rat Cortical Neurons

  • Meiqun Sun
  • Hongli Liu
  • Huanbai Xu
  • Hongtao Wang
  • Xiaojing WangEmail author
Original Paper
  • 232 Downloads

Abstract

Seizure activity is linked to astrocyte activation as well as dysfunctional cortical neuron excitability produced from changes in calcium-activated potassium (KCa) channel function. Ciliary neurotrophic factor-treated astrocyte conditioned medium (CNTF-ACM) can be used to investigate the peripheral effects of activated astrocytes upon cortical neurons. However, CNTF-ACM’s effect upon KCa channel activity in cultured cortical neurons has not yet been investigated. Whole-cell patch clamp recordings were performed in rat cortical neurons to evaluate CNTF-ACM’s effects upon charybdotoxin-sensitive large-conductance KCa (BK) channel currents and apamin-sensitive small-conductance KCa (SK) channel current. Biotinylation and RT-PCR were applied to assess CNTF-ACM’s effects upon the protein and mRNA expression, respectively, of the SK channel subunits SK2 and SK3 and the BK channel subunits BKα1 and BKβ3. An anti-fibroblast growth factor-2 (FGF-2) monoclonal neutralizing antibody was used to assess the effects of the FGF-2 component of CNTF-ACM. CNTF-ACM significantly increased KCa channel current density, which was predominantly attributable to gains in BK channel activity (p < 0.05). CNTF-ACM produced a significant increase in BKα1 and BKβ3 expression (p < 0.05) but had no significant effect upon SK2 or SK3 expression (p > 0.05). Blocking FGF-2 produced significant reductions in KCa channel current density (p > 0.05) as well as BKα1 and BKβ3 expression in CNTF-ACM-treated neurons (p > 0.05). CNTF-ACM significantly enhances BK channel activity in rat cortical neurons and that FGF-2 is partially responsible for these effects. CNTF-induced astrocyte activation results in secretion of neuroactive factors which may affect neuronal excitability and resultant seizure activity in mammalian cortical neurons.

Keywords

Ciliary neurotrophic factor, CNTF Calcium-activated potassium channel 

Notes

Acknowledgments

This work was supported by the National Natural Science Foundation of China (Grant No. 81171117), the Scientific Research Starting Foundation for the Returned Overseas Chinese Scholars (Chinese Ministry of Education, Grant No. 44), and the Science and Technology Program of Anhui Province (a Key Laboratory Project, Grant No. 1506c085014).

Author Contributions

X. J. W.: Conceived and designed the study. M. Q. S., H. L. L., H. B. X., and H. T. W: Performed the experiments. X. J. W.: Analyzed the data and drafted the manuscript

Compliance with Ethical Standards

Conflict of interest

None.

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Meiqun Sun
    • 2
  • Hongli Liu
    • 3
  • Huanbai Xu
    • 4
  • Hongtao Wang
    • 5
  • Xiaojing Wang
    • 1
    Email author
  1. 1.Department of Respiration, Anhui Clinical and Preclinical Key Laboratory of Respiratory DiseaseThe First Affiliated Hospital of Bengbu Medical CollegeBengbuChina
  2. 2.Department of Histology and EmbryologyBengbu Medical CollegeBengbuChina
  3. 3.Department of Gynecological OncologyThe First Affiliated Hospital of Bengbu Medical CollegeBengbuChina
  4. 4.Department of Endocrinology and MetabolismShanghai Jiaotong University Affiliated First People’s HospitalShanghaiChina
  5. 5.Department of ImmunologyBengbu Medical CollegeBengbuChina

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