Premium
Membrane Stretch‐Induced Activation of TRPM4 in Cerebral Artery Smooth Muscle Cells
Author(s) -
Yang Ying,
Gonzales Albert L,
Sanders Lindsey,
Earley Scott
Publication year - 2012
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.26.1_supplement.685.35
Subject(s) - transient receptor potential channel , mechanosensitive channels , phospholipase c , chemistry , patch clamp , biophysics , depolarization , microbiology and biotechnology , endoplasmic reticulum , myocyte , channel blocker , ion channel , receptor , biochemistry , biology , calcium , organic chemistry
In cerebral artery smooth muscle cells (SMCs), the melastatin transient receptor potential (TRP) channel TRPM4 is a crucial mediator of pressure‐induced membrane depolarization, and is activated by Ca 2+ released from inositol trisphosphate (IP 3 ) receptors located on the sarcoplasmic reticulum. In the current study, we examined the mechanosensitivity of TRPM4 channels in native SMCs. TRPM4 channel activity was recorded under perforated patch clamp conditions as the plasma membrane was stretched by applying suction to the patch pipette. Increases in cation current proportional to the magnitude of applied suction were recorded. Mechanosensitive currents were inhibited by the selective TRPM4 blocker 9‐phenenthral but were unaffected by the BK Ca channel blocker paxilline. Phospholipase C (PLC) cleaves the membrane phospholipid phosphatidylinositol 4,5‐bisphosphate (PIP 2 ) into IP 3 and diacylglycerol (DAG). Prior studies suggest that mechanical stress can stimulate PLC activity. Therefore, we tested the hypothesis that PLC activity is necessary for plasma membrane stretch‐induced activation of TRPM4 in cerebral artery myocytes. We find that the PLC blocker U73122 inhibits stretch‐induced TRPM4 activation, suggesting that PLC plays an important role in activation of TRPM4 by mechanical stimulus in cerebral artery smooth muscle cells. RO1HL091905(SE); F31HL094145‐01(AG).