Document Detail

Two distinct signaling pathways for regulation of spontaneous local Ca2+ release by phospholipase C in airway smooth muscle cells.
MedLine Citation:
PMID:  17093969     Owner:  NLM     Status:  MEDLINE    
Spontaneous local Ca(2+) release events have been observed in airway smooth muscle cells (SMCs), but the underlying mechanisms are largely unknown. Considering that each type of SMCs may use its own mechanisms to regulate local Ca(2+) release events, we sought to investigate the signaling pathway for spontaneous local Ca(2+) release events in freshly isolated mouse airway SMCs using a laser scanning confocal microscope. Application of ryanodine to block ryanodine receptors (RyRs) abolished spontaneous local Ca(2+) release events, indicating that these events are RyR-mediated Ca(2+) sparks. Inhibition of inositol 1,4,5-triphosphate receptors (IP(3)Rs) by 2-aminoethoxydiphenyl-borate (2-APB) or xestospongin-C significantly blocked the activity of Ca(2+) sparks. Under patch clamp conditions, dialysis of IP(3) to activate IP(3)Rs increased the activity of local Ca(2+) events in control cells but had no effect in ryanodine-pretreated cells. The RyR agonist caffeine augmented the frequency of Ca(2+) sparks in cells pretreated with and without 2-APB or xestospongin-C. The specific phospholipase C (PLC) blocker U73122 decreased the activity of Ca(2+) sparks and prevented xestospongin-C from producing the inhibitory effect. The protein kinase C (PKC) activator 1-oleoyl-2-acetyl-glycerol or phorbol-12-myristate-13-acetate inhibited Ca(2+) sparks, whereas the PKC inhibitor chelerythrine, PKCvarepsilon inhibitory peptide, or PKCvarepsilon gene knockout produced an opposite effect. Collectively, our data suggest that the basal activation of PLC regulates the activity of RyR-mediated, spontaneous Ca(2+) sparks in airway SMCs through two distinct signaling pathways: a positive IP(3)-IP(3)R pathway and a negative diacylglycerol-PKCvarepsilon pathway.
Qing-Hua Liu; Yun-Min Zheng; Yong-Xiao Wang
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2006-11-09
Journal Detail:
Title:  Pflügers Archiv : European journal of physiology     Volume:  453     ISSN:  0031-6768     ISO Abbreviation:  Pflugers Arch.     Publication Date:  2007 Jan 
Date Detail:
Created Date:  2006-12-20     Completed Date:  2007-06-11     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0154720     Medline TA:  Pflugers Arch     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  531-41     Citation Subset:  IM    
Center for Cardiovascular Sciences, Albany Medical College (MC-8), 47 New Scotland Avenue, Albany, NY 12208, USA.
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MeSH Terms
Alkaloids / pharmacology
Benzophenanthridines / pharmacology
Boron Compounds / pharmacology
Caffeine / pharmacology
Calcium / metabolism*
Cells, Cultured
Diglycerides / pharmacology
Estrenes / pharmacology
Inositol 1,4,5-Trisphosphate / metabolism
Inositol 1,4,5-Trisphosphate Receptors / antagonists & inhibitors,  physiology
Macrocyclic Compounds / pharmacology
Myocytes, Smooth Muscle / drug effects,  metabolism*
Oxazoles / pharmacology
Pyrrolidinones / pharmacology
Respiratory System / cytology,  drug effects,  metabolism
Ryanodine / pharmacology
Ryanodine Receptor Calcium Release Channel / metabolism,  physiology
Sarcoplasmic Reticulum / drug effects,  metabolism
Signal Transduction / drug effects,  physiology*
Type C Phospholipases / antagonists & inhibitors,  metabolism*
Reg. No./Substance:
0/2-aminoethoxydiphenyl borate; 0/Alkaloids; 0/Benzophenanthridines; 0/Boron Compounds; 0/Diglycerides; 0/Estrenes; 0/Inositol 1,4,5-Trisphosphate Receptors; 0/Macrocyclic Compounds; 0/Oxazoles; 0/Pyrrolidinones; 0/Ryanodine Receptor Calcium Release Channel; 0/xestospongin C; 112648-68-7/1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; 15662-33-6/Ryanodine; 34316-15-9/chelerythrine; 58-08-2/Caffeine; 7440-70-2/Calcium; 85166-31-0/Inositol 1,4,5-Trisphosphate; 86390-77-4/1-oleoyl-2-acetylglycerol; EC 3.1.4.-/Type C Phospholipases

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