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PKA Enhances the Sensitivity of IP 3 Receptors in Swine Airway Submucosal Gland Cells.
Author(s) -
LU SILU,
FARLEY JERRY M
Publication year - 2009
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.23.1_supplement.580.4
Subject(s) - forskolin , receptor , chemistry , patch clamp , vasoactive intestinal peptide , carbachol , medicine , endocrinology , sensitization , biophysics , biology , neuropeptide , biochemistry , immunology
Increased sensitivity of airway submucosal gland cells (SMGC) to ACh by PKA activation results in increased transepithelial ion movement. The mechanism of the increased sensitivity induced by PKA is unclear. Since ACh‐induced transepithelial ion movement is dependent on the IP 3 /Ca 2+ signaling pathway, we hypothesized that PKA enhances sensitivity of IP 3 receptors in airway SMGC, resulting in increased [Ca 2+ ] i . Patch clamp of swine airway SMGC was performed in these studies. We showed that forskolin decreased the EC 50 for IP 3 about 4‐fold measured as the peak K Ca current induced upon whole cell formation with IP 3 in the pipette. VIP (10 nM), a co‐neurotransmitter present in cholinergic airway nerve fibers, enhanced the response to 0.3 µM IP 3 . Neither VIP nor IP 3 (0.3 µM) induced K Ca current when applied alone. VIP induced a significant K Ca current in SMGC only when the internal solution contained IP 3 . Removing external Ca 2+ did not abolish the VIP‐induced sensitization of the peak IP 3 response although the plateau response was lost. This suggests that Ca 2+ release is sensitized as well as Ca 2+ influx. Elevating external Ca 2+ to 5 mM revealed a K Ca current induced only in the presence of IP 3 (0.3 µM). Thus Ca 2+ entry may also be increased by IP 3 (0.3 µM). These results suggest that PKA increases the sensitivity of IP 3 receptors by phosphorylation, resulting in the increased intracellular Ca 2+ release and Ca 2+ entry.