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Novel findings in membrane depolarization‐induced force development in vascular smooth muscle (865.11)
Author(s) -
Ets Hillevi,
Moreland Robert
Publication year - 2014
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.28.1_supplement.865.11
Subject(s) - bay k8644 , protein kinase c , chemistry , kinase , nifedipine , vascular smooth muscle , depolarization , microbiology and biotechnology , biophysics , biology , endocrinology , smooth muscle , calcium , biochemistry , organic chemistry
A unique phenomenon of vascular smooth muscle (VSM) is its ability to maintain force for a prolonged period of time. The exact mechanism responsible is not known but studies suggest a critical role for L‐type Ca2+ channels (LTCC). The purpose of this study was to investigate the consequences of prolonged LTCC opening with an agonist, Bay K8644, to elucidate the intracellular mechanisms responsible for maintaining VSM tone. Smooth muscle tissue isolated from swine carotid arteries was mounted for isometric force recording. Tissues were stimulated with Bay K8644 alone or following pretreatment with one of the following inhibitors: nifedipine (LTCC), ML‐7 (MLC kinase), bisindolylmaleimide (PKC), U0126 (MAP kinase), or H‐1152 (Rho kinase). The following results were obtained: • Bay K8644 increased MLC phosphorylation, PKC activity, MAP kinase activity, and force development but partially inhibited ROCK activity; CPI‐17 phosphorylation was not changed. • Bay K8644‐dependent activation of PKC inhibited MAP kinase activity; the Bay K8644 partial inhibition of ROCK activity was reversed by inhibition of LTCC with nifedipine . • Inhibition of MAP kinase activity significantly increased MLC kinase activity and inhibition of MLC kinase activity greatly increased MAP kinase activity. These results indicate that the maintenance of force in VSM involves an intricate signaling network with multiple modulatory steps.