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Pharmacological profile of store‐operated channels in cerebral arteriolar smooth muscle cells
Author(s) -
Flemming R,
Xu S Z,
Beech D J
Publication year - 2003
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0705327
Subject(s) - cyclopiazonic acid , thapsigargin , nifedipine , ruthenium red , chemistry , wortmannin , voltage dependent calcium channel , vascular smooth muscle , biophysics , calcium , endocrinology , phosphatidylinositol , biochemistry , biology , intracellular , smooth muscle , signal transduction , organic chemistry
In this study, we determined a pharmacological profile of store‐operated channels (SOCs) in smooth muscle cells of rabbit pial arterioles. Ca 2+ ‐indicator dyes, fura‐PE3 or fluo‐4, were used to track [Ca 2+ ] i and 10 μ M methoxyverapamil (D600) was present in all experiments on SOCs to prevent voltage‐dependent Ca 2+ entry. Store depletion was induced using thapsigargin or cyclopiazonic acid. SOC‐mediated Ca 2+ entry was inhibited concentration dependently by Gd 3+ (IC 50 101 n M ). It was also inhibited by 10 μ M La 3+ (70% inhibition, N =5), 100 μ M Ni 2+ (57% inhibition, N =5), 75 μ M 2‐aminoethoxydiphenylborate (66% inhibition, N =4), 100 μ M capsaicin (12% inhibition, N =3) or preincubation with 10 μ M wortmannin (76% inhibition, N =4). It was completely resistant to 1 μ M nifedipine ( N =5), 10 μ M SKF96365 ( N =6), 10 μ M LOE908 ( N =14), 10–100 μ M ruthenium red ( N =1+2), 100 μ M sulindac ( N =4), 0.5 m M streptomycin ( N =3) or 1 : 10,000 dilution Grammostolla spatulata venom ( N =4). RT–PCR experiments on isolated arteriolar fragments showed expression of mRNA species for TRPC1, 3, 4, 5 and 6. The pharmacological profile of SOC‐mediated Ca 2+ entry in arterioles supports the hypothesis that these SOCs are distinct from tonically active background channels and several store‐operated and other nonselective cation channels described in other cells. Similarities with the pharmacology of TRPC1 support the hypothesis that TRPC1 is a subunit of the arteriolar smooth muscle SOC.>British Journal of Pharmacology (2003) 139 , 955–965. doi: 10.1038/sj.bjp.0705327