Pharmacological profile of store-operated channels in cerebral arteriolar smooth muscle cells
Article first published online: 30 JAN 2009
2003 British Pharmacological Society
British Journal of Pharmacology
Volume 139, Issue 5, pages 955–965, July 2003
How to Cite
Flemming, R., Xu, S. Z. and Beech, D. J. (2003), Pharmacological profile of store-operated channels in cerebral arteriolar smooth muscle cells. British Journal of Pharmacology, 139: 955–965. doi: 10.1038/sj.bjp.0705327
- Issue published online: 30 JAN 2009
- Article first published online: 30 JAN 2009
- (Received March 4, 2003, Accepted March 24, 2003)
- Calcium stores;
- calcium channels;
- store-operated channels;
- cerebral arteriole;
- smooth muscle
In this study, we determined a pharmacological profile of store-operated channels (SOCs) in smooth muscle cells of rabbit pial arterioles. Ca2+-indicator dyes, fura-PE3 or fluo-4, were used to track [Ca2+]i and 10 μM methoxyverapamil (D600) was present in all experiments on SOCs to prevent voltage-dependent Ca2+ entry. Store depletion was induced using thapsigargin or cyclopiazonic acid.
SOC-mediated Ca2+ entry was inhibited concentration dependently by Gd3+ (IC50 101 nM). It was also inhibited by 10 μM La3+ (70% inhibition, N=5), 100 μM Ni2+ (57% inhibition, N=5), 75 μM 2-aminoethoxydiphenylborate (66% inhibition, N=4), 100 μM capsaicin (12% inhibition, N=3) or preincubation with 10 μM wortmannin (76% inhibition, N=4). It was completely resistant to 1 μM nifedipine (N=5), 10 μM SKF96365 (N=6), 10 μM LOE908 (N=14), 10–100 μM ruthenium red (N=1+2), 100 μM sulindac (N=4), 0.5 mM 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 Ca2+ 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