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Forskolin induced actin depolymerization and force inhibition in porcine coronary artery
Author(s) -
Komalavilas Padmini,
Hocking Kyle M,
Putumbaka Gowthami,
Venkatraman Sneha L,
CheungFlynn Joyce,
Brophy Colleen M
Publication year - 2011
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.25.1_supplement.1115.3
Subject(s) - forskolin , actin , contractility , chemistry , myosin light chain kinase , phosphorylation , phalloidin , microbiology and biotechnology , histamine , biophysics , biology , endocrinology , biochemistry , cytoskeleton , receptor , cell
Actin polymerization plays an important role in the regulation of contractility of smooth muscle; however, the mechanism by which actin polymerization affects contractility is still less understood. The role of thin filament regulation of smooth muscle contractility was examined in porcine coronary artery (PCA). PCA was pretreated with 5μM forskolin, a vasodilator, followed by 5μM histamine, a vasoconstrictor. Force and intracellular [Ca 2+ ] levels were concurrently measured in a Fluroplex ‐Tissue Bath Fluorometry System. Filamentous (F) and globular (G) actin levels as well as phosphorylation of proteins were determined in frozen rings. Forskolin completely inhibited histamine‐induced force development in PCA without significantly changing myosin light chain phosphorylation or intracellular [Ca 2+ ]. However, forskolin inhibited the increase in F actin concentration induced by histamine. Forskolin pretreatment led to increases in the phosphorylation of heat shock‐related protein 20 (HSPB6), vasodilator‐stimulated phosphoprotein (VASP) and was associated with dephosphorylation of the actin depolymerizing factor, cofilin. Forskolin also inhibited histamine‐induced phosphorylation of paxillin, a focal adhesion protein. These results suggest that forskolin‐induced force inhibition of PCA involves thin filament rather than thick filament regulation. Support by NIH RO1Grant and VA Merit.