HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Duffy, S. M. Articles by Bradding, P. Search for Related Content PubMed PubMed Citation Articles by Duffy, S. M. Articles by Bradding, P. Pubmed/NCBI databases Compound via MeSH Substance via MeSH

Resting and Activation-Dependent Ion Channels in Human Mast Cells¹

Division of Respiratory Medicine, Institute for Lung Health, University of Leicester, Leicester, United Kingdom

The mechanism of mediator secretion from mast cells in disease is likely to include modulation of ion channel activity. Several distinct Ca²⁺, K⁺, and Cl^- conductances have been identified in rodent mast cells, but there are no data on human mast cells. We have used the whole-cell variant of the patch clamp technique to characterize for the first time macroscopic ion currents in purified human lung mast cells and human peripheral blood-derived mast cells at rest and following IgE-dependent activation. The majority of both mast cell types were electrically silent at rest with a resting membrane potential of around 0 mV. Following IgE-dependent activation, >90% of human peripheral blood-derived mast cells responded within 2 min with the development of a Ca²⁺-activated K⁺ current exhibiting weak inward rectification, which polarized the cells to around -40 mV and a smaller outwardly rectifying Ca²⁺-independent Cl^- conductance. Human lung mast cells showed more heterogeneity in their response to anti-IgE, with Ca²⁺-activated K⁺ currents and Ca²⁺-independent Cl^- currents developing in 50% of cells. In both cell types, the K⁺ current was blocked reversibly by charybdotoxin, which along with its electrophysiological properties suggests it is carried by a channel similar to the intermediate conductance Ca²⁺-activated K⁺ channel. Charybdotoxin did not consistently attenuate histamine or leukotriene C₄ release, indicating that the Ca²⁺-activated K⁺ current may enhance, but is not essential for, the release of these mediators.

This article has been cited by other articles:

				M. Sobiesiak, E. Shumilina, R. S. Lam, F. Wolbing, N. Matzner, S. Kaesler, I. M. Zemtsova, A. Lupescu, N. Zahir, D. Kuhl, et al. Impaired Mast Cell Activation in Gene-Targeted Mice Lacking the Serum- and Glucocorticoid-Inducible Kinase SGK1 J. Immunol., October 1, 2009; 183(7): 4395 - 4402. [Abstract] [Full Text] [PDF]

				E. Shumilina, R. S. Lam, F. Wolbing, N. Matzner, I. M. Zemtsova, M. Sobiesiak, H. Mahmud, U. Sausbier, T. Biedermann, P. Ruth, et al. Blunted IgE-Mediated Activation of Mast Cells in Mice Lacking the Ca2+-Activated K+ Channel KCa3.1 J. Immunol., June 15, 2008; 180(12): 8040 - 8047. [Abstract] [Full Text] [PDF]

				M. C. Shepherd, S. M. Duffy, T. Harris, G. Cruse, M. Schuliga, C. E. Brightling, C. B. Neylon, P. Bradding, and A. G. Stewart KCa3.1 Ca2+Activated K+ Channels Regulate Human Airway Smooth Muscle Proliferation Am. J. Respir. Cell Mol. Biol., November 1, 2007; 37(5): 525 - 531. [Abstract] [Full Text] [PDF]

				R. C. E. Wykes, M. Lee, S. M. Duffy, W. Yang, E. P. Seward, and P. Bradding Functional Transient Receptor Potential Melastatin 7 Channels Are Critical for Human Mast Cell Survival J. Immunol., September 15, 2007; 179(6): 4045 - 4052. [Abstract] [Full Text] [PDF]

				E. D. Giudice, L. Rinaldi, M. Passarotto, F. Facchinetti, A. D'Arrigo, A. Guiotto, M. D. Carbonare, L. Battistin, and A. Leon Cannabidiol, unlike synthetic cannabinoids, triggers activation of RBL-2H3 mast cells J. Leukoc. Biol., June 1, 2007; 81(6): 1512 - 1522. [Abstract] [Full Text] [PDF]

				G Cruse, S M Duffy, C E Brightling, and P Bradding Functional KCa3.1 K+ channels are required for human lung mast cell migration Thorax, October 1, 2006; 61(10): 880 - 885. [Abstract] [Full Text] [PDF]

				G. Cruse, D. Kaur, W. Yang, S. M. Duffy, C. E. Brightling, and P. Bradding Activation of human lung mast cells by monomeric immunoglobulin E Eur. Respir. J., May 1, 2005; 25(5): 858 - 863. [Abstract] [Full Text] [PDF]

				E. Aneiros, S. Philipp, A. Lis, M. Freichel, and A. Cavalie Modulation of Ca2+ Signaling by Na+/Ca2+ Exchangers in Mast Cells J. Immunol., January 1, 2005; 174(1): 119 - 130. [Abstract] [Full Text] [PDF]

				P. Bradding, Y. Okayama, N. Kambe, and H. Saito Ion channel gene expression in human lung, skin, and cord blood-derived mast cells J. Leukoc. Biol., May 1, 2003; 73(5): 614 - 620. [Abstract] [Full Text] [PDF]