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This Article Full Text Full Text (PDF) All Versions of this Article: 296/3/L453    most recent 90467.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Gu, Q. Articles by Lee, L.-Y. Search for Related Content PubMed PubMed Citation Articles by Gu, Q. Articles by Lee, L.-Y.

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

¹Department of Physiology, University of Kentucky Medical Center, Lexington, Kentucky; ²Departments of Dermatology and Medicine, University of Utah, Salt Lake City, Utah

Submitted 3 September 2008 ; accepted in final form 4 January 2009

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 (IK_dr) and the A-type, fast-inactivating K⁺ current (IK_a) in these sensory neurons. In conclusion, our results indicate that the inhibition of IK_dr and IK_a 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.

eosinophil granule proteins; transient receptor potential vanilloid type-1 receptor; voltage-gated K⁺ channel; patch clamp