Mechanisms of eosinophil major basic protein-induced hyperexcitability of vagal pulmonary chemosensitive neurons

Qihai Gu, Michelle E. Lim, Gerald J. Gleich, Lu Yuan Lee

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

We have reported recently that eosinophil-derived basic proteins directly enhance the capsaicin- and electrical stimulation-evoked whole cell responses in rat pulmonary sensory neurons (19). Our present study further elucidates the mechanisms underlying the sensitization of pulmonary afferent nerves induced by these cationic proteins. Our results show that pretreatment with eosinophil major basic protein (MBP; 2 μM, 60 s) significantly enhanced the excitability of isolated rat vagal pulmonary chemosensitive neurons to acid and ATP in the current-clamp mode, but this potentiating effect was absent in the voltage-clamp recordings. The hyperexcitability induced by MBP was not prevented by the blockade of either transient receptor potential vanilloid type-1 receptor (TRPV1) selectively (inhibitor: AMG 9810; 1 μM, 2 min) or all TRPV1-4 channels (inhibitor: ruthenium red; 5 μM, 2 min). In addition, MBP also markedly potentiated the excitability of mouse pulmonary chemosensitive neurons, and no detectable difference was found between those isolated from wild-type and TRPV1 knockout mice. Furthermore, MBP pretreatment affected the decay time and recovery phase of the action potentials evoked by current injections and significantly inhibited both the sustained delayed-rectifier voltage-gated K+ current (IKdr) and the A-type, fast-inactivating K + current (IKa) in these sensory neurons. In conclusion, our results indicate that the inhibition of IKdr and IKa should, at least in part, account for the hyperexcitability of pulmonary chemosensitive neurons induced by eosinophil-derived cationic proteins, whereas an interaction with TRPV1 channels does not seem to be required for the sensitizing effect of these proteins.

Original languageEnglish
Pages (from-to)L453-L461
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume296
Issue number3
DOIs
StatePublished - Mar 2009

Keywords

  • Eosinophil granule proteins
  • Patch clamp
  • Transient receptor potential vanilloid type-1 receptor
  • Voltage-gated K channel

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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