Premium
PLC gamma‐1 is Required for IP3‐mediated Activation of TRPM4 and Pressure‐Induced Depolarization and Vasoconstriction in Cerebral Arteries
Author(s) -
Garcia Zarine,
Earley Scott
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.1024.16
Subject(s) - transient receptor potential channel , vasoconstriction , depolarization , chemistry , vascular smooth muscle , cerebral arteries , trpc , myocyte , inositol , inositol trisphosphate , microbiology and biotechnology , medicine , endocrinology , biology , biochemistry , receptor , smooth muscle
In cerebral artery smooth muscle cells (SMCs), the melastatin transient receptor potential (TRP) channel TRPM4 is activated by intracellular Ca 2+ release from inositol trisphosphate (IP 3 ) receptors located on the sarcoplasmic reticulum. IP 3 is a product of phospolipase C (PLC), an enzyme which cleaves the membrane phospholipid phosphatidylinositol 4,5‐biphosphate (PIP 2 ) into IP 3 and diacylglycerol (DAG). Multiple isoforms of PLC are present in vascular smooth muscle and can be classified into one of three families – β, γ, or δ. This study tested the hypothesis that PLC activity is required for TRPM4 activation, and investigated the particular PLC isoform responsible. Patch clamp electrophysiology recordings from freshly isolated cerebral myocytes revealed that the PLC inhibitor U‐73122 decreased the total open probability (NP o ) of transient inward cation currents (TICCs) associated with TRPM4 by ~75%, while its inactive analog, U‐73343, had no effect. In addition, siRNA‐mediated knockdown of the PLCγ 1 isoform decreased the TICC NP o . Following knockdown of PLCγ 1 , we also found that pressure‐induced SMC depolarization and myogenic vasoconstriction of cerebral arteries were greatly diminished compared with controls. These data suggest that PLCγ 1 generates the IP 3 required for TRPM4 activation in cerebral myocytes, and pressure‐induced SMC depolarization and vasoconstriction. RO1HL091905