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IL‐4 inhibits calcium transients in bovine trachealis cells by a ryanodine receptor dependent mechanism
Author(s) -
Ethier Michael F.,
Madison J. Mark
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.05-4031fje
Subject(s) - ryanodine receptor , ionomycin , calcium , trachealis muscle , carbachol , chemistry , endocrinology , fura 2 , calcium in biology , medicine , cyclic adp ribose , stimulation , extracellular , biophysics , cytosol , biochemistry , biology , microbiology and biotechnology , cd38 , charybdotoxin , enzyme , stem cell , cd34
IL‐4 and IL‐13 have important roles in the pathogenesis of asthma. A novel finding was that brief exposure of airway smooth muscle cells to IL‐4 inhibited carbachol‐stimulated calcium transients. We hypothesized that IL‐4 inhibits transients by decreasing calcium store content and tested this by measuring the effects of IL‐4 on transients induced by a nonspecific ionophore. Bovine trachealis cells were loaded with fura 2‐AM, and cytosolic calcium concentrations ([Ca 2+ ]i) were measured in single cells by digital microscopy. Stimulation (S1) with carbachol (10 μM) caused rapid, transient increases in [Ca 2+ ]i to 1299 ± 355 nM ( n =5). After recovery of calcium stores, stimulation (S2) of the same cells with ionomycin (10 μM), in the absence of extracellular calcium, also increased [Ca 2+ ]i to give S2/S1 ratio of 1.03 ± 0.29. However, after 20 min of IL‐4 (50 ng/ml), but not IL‐13, ionomycin transients were decreased to 0.50 ± 0.16 (S2/S1, P =0.02, n =6). IL‐4 did not inhibit transients with ryanodine receptor calcium release channels (RyR) blocked by ryanodine (200 μM) (S2/S1=1.01±0.11) but still did in the presence of 8‐bromo cyclic ADP‐ribose, an antagonist of cyclic ADP‐ribose (cADPR) signaling at RyR (S2/S1=0.48±0.13). Together, findings suggest that IL‐4 decreases intracellular calcium stores by mechanisms dependent on RyR, but not on cADPR signaling.