|
|
||||||||
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:
![]() |
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] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |