Tumor Necrosis Factor Alpha Inhibits L-Type Ca2+ Channels in Sensitized Guinea Pig Airway Smooth Muscle through ERK 1/2 Pathway
TNF-α diminishes the L-type Ca2+ currents through activation of the TNF-α receptor 1 (TNFR1) and MAP kinase signaling pathway in guinea pig tracheal myocytes. (a) Myocytes from nonsensitized animals (NS) grown with fetal bovine serum (FBS) showed an inward Ba2+ current. This current was reduced when NS myocytes were grown with serum from sensitized guinea pig (Ser-S, 10%). This decrease was abolished when the small-molecule inhibitor of TNF-α (SMI-TNF, ), which impedes this cytokine from binding to its receptor, was incubated during cell growth. (b) The Ba2+ current diminution induced by Ser-S incubation in NS myocytes was also reversed, in a concentration dependent manner, by the TNFR1 antagonist (WP9QY, ). (c) The Ba2+ current decrease induced by Ser-S was abolished when myocytes were incubated with an inhibitor of ERK 1/2 kinase (U0126, ). Insets in each figure represent original recordings. , , when compared with NS + Ser-S group. Symbols represent mean ± SEM.
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