Document Detail


TRPC3 Channel Contributes to Nitric Oxide Release: Significance Under Normoxia and Hypoxia-Reoxygenation.
MedLine Citation:
PMID:  21493700     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Aims: Intracellular Ca(2+) ([Ca(2+)](i)) regulation in endothelial cells depends on transient receptor potential channels (TRPs) and the role of canonical TRPs (TRPCs) under hypoxia-reoxygenation (H-R) is unclear. We hypothesized that TRPC3 contributes to endothelial nitric oxide (NO) release and that H-R may reduce TRPC3 activity and the associated endothelial function including NO release. Methods & Results: [Ca(2+)](i) measurements and patch-clamp study in primary cultured porcine coronary endothelial cells (PCECs), measurements of NO and endothelium-dependent relaxation in porcine coronary arteries, and RT-PCR and Western-blot were conducted. Pretreatment with SKF96365 (inhibitor of TRPCs) or selective TRPC3 inhibitor Pyr3 significantly decreased bradykinin-induced vasorelaxation. One-hour hypoxia followed by reoxygenation significantly reduced the vasorelaxation (70.3±6.4% vs. 88.9±3.5%) and NO concentration (24.0±1.3 vs. 45.2±2.8 nmol/L) that were restored by pre-incubation with TRPC3/6/7 activator 1-oleoyl-2-acetyl-sn-glycerol (96.4±1.8%, 41.1±4.7 nmol/L). In PCECs, H-R inhibited bradykinin-activated membrane current (8.6±0.4 vs. 14.0±1.5 pA/pF) and Pyr3-sensitive TRPC3 current (3.8±0.3 vs. 6.3±0.6 pA/pF) (p<0.01). H-R also inhibited bradykinin-induced Ca(2+) influx and the Ca(2+) influx via TRPC3. Cell surface expression of TRPC3 was decreased after H-R. Conclusions: We have for the first time demonstrated that Ca(2+) entry via endothelial TRPC3 contributes to NO release and have revealed that H-R is associated with inhibition of TRPC3 activity. Inhibition of channel trafficking to cell surface is involved in the underlying mechanism of the decrease of TRPC3 current and the reduction in Ca(2+) entry through TRPC3 during H-R. This study suggests that TRPC3 may have the potential to be a new target for endothelial protection during H-R.
Authors:
Jun-Hao Huang; Guo-Wei He; Hong-Mei Xue; Xiao-Qiang Yao; Xiao-Cheng Liu; Malcolm John Underwood; Qin Yang
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-4-14
Journal Detail:
Title:  Cardiovascular research     Volume:  -     ISSN:  1755-3245     ISO Abbreviation:  -     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-4-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Surgery, The Chinese University of Hong Kong, Hong Kong & TEDA International Cardiovascular Hospital, Medical College, Nankai University, Tianjin, China.
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