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PGE2 enhances Ca2+‐dependent ionic currents in the airway mucus gland cells
Author(s) -
Liu Huiling,
Kanyicska Bela,
Farley Jerry M
Publication year - 2007
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/fasebj.21.6.a1170-a
Subject(s) - bumetanide , chemistry , biophysics , patch clamp , endocrinology , trpc , forskolin , medicine , receptor , ion transporter , microbiology and biotechnology , transient receptor potential channel , biology , biochemistry , membrane
Airway submucosal gland cell (SMGC) secretions are under the control of various secretagogues. Mechanisms of interactions between PGE 2 and ACh in activating mucus cell ion current responses are examined in this study. PGE 2 pretreatment sensitized ACh‐induced short‐circuit current (I SC ) that were mediated by EP 2 receptors and mimicked by forskolin. PKA inhibitors, 14–22 amide PKI (PKI) and Rp‐cAMPs, prevented the effect of PGE 2 . Treatment with 0 [Ca 2+ ] o or Ca 2+ entry blocker, SKF96365 , shifted the ACh concentration‐response relationships to the right, but did not abolish PGE 2 ‐induced sensitization of the ACh response. An IP 3 receptor antagonist and the Ca 2+ entry blocker, 2‐APB, abolished the ACh‐induced response. Under whole‐cell patch clamp, IP 3 , dialyzed in the cytosol via patch pipette upon whole‐cell formation, induced immediate increases in both KCa and CaCC currents that were prolonged by simultaneous inclusion of cAMP in the internal solution. The plateau phases of both currents were related to Ca 2+ entry, abolishable by treatments with 0 [Ca 2+ ] o , Gd 3+ , 2‐APB, or SKF96365 , and were also enhanced by membrane hyperpolarization. Abundant mRNA expressions for TRPC channels (TRPC‐1>>3≈6>4) were detected in the mucus cells using real‐time RT‐PCR. Thus, PGE 2 , via EP 2 receptors and the cAMP/PKA pathway, enhances ACh‐induced, Ca 2+ ‐mediated ionic currents in mucus cells through activating Ca 2+ ‐entry independent mechanisms that are primarily responsible for sensitization of the ACh response. ACh‐induced Ca 2+ entry via non‐selective cation channels was also enhanced by cAMP treatment, important for sustaining the ACh‐induced response [Supported by a grant from the American Heart Association to J.M.F.].