Premium
Impaired c‐src kinase regulation of muscle contraction during colonic inflammation is due to nitrosylation of Ca 2+ channels
Author(s) -
Ross Gracious R,
Kang Minho,
Drozd Mary,
Akbarali Hamid I
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.a1156-b
Subject(s) - chemistry , contraction (grammar) , inflammation , peroxynitrite , endocrinology , medicine , nitrotyrosine , calcium , muscle contraction , biochemistry , biology , nitric oxide , nitric oxide synthase , enzyme , superoxide
Basal levels of c‐src kinase (pp60) are known to regulate smooth muscle Ca 2+ channels. Colonic inflammation results in attenuated Ca 2+ currents and muscle contraction. Here, we examined the role of pp60 in experimental colitis. Ca 2+ ‐influx induced contractions were measured by isometric tension recordings of mouse colonic longitudinal muscle strips depolarized by high K + . The E max to CaCl 2 was significantly less in inflamed tissues (38.4 ± 7.6%) than controls. The EC 50 for CaCl 2 was 1.2 × 10 −4 M in controls and 2.4 × 10 −4 M in inflamed tissues indicative of reduced Ca 2+ influx. PP2, a selective pp60 inhibitor, significantly reduced the contractile amplitude and shifted the pD 2 from 3.88 to 2.44 in controls while it was ineffective in inflamed tissues (3.66 vs 3.43). Following pretreatment with a SIN‐1/peroxynitrite combination the maximal contraction to CaCl 2 was reduced by 46 ± 7% in controls but unaffected in inflamed (13 ± 11%). Peroxynitrite also prevented the inhibitory effect of PP2 in control tissues. Neither the Ca 2+ channel, Ca v 1.2b, gene expression (real –time PCR) nor the pp60 activity were altered by inflammation. Western analysis with 3‐nitrotyrosine antibody revealed nitrotyrosylation of Ca 2+ channel proteins by inflammation. These data suggest that posttranslational modification of Ca 2+ channels, possibly nitrotyrosylation, prevents c‐src kinase regulation resulting in decreased Ca 2+ influx. Supported by NIDDK46367