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Mechanism of asynchronous Ca 2+ waves underlying agonist‐induced contraction in the rat basilar artery
Author(s) -
Syyong HT,
Yang HHC,
Trinh G,
Cheung C,
Kuo KH,
Van Breemen C
Publication year - 2009
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 - 10.1111/j.1476-5381.2008.00063.x
Subject(s) - ryanodine receptor , chemistry , uridine triphosphate , contraction (grammar) , biophysics , cyclopiazonic acid , muscle contraction , medicine , basilar artery , vascular smooth muscle , endocrinology , endoplasmic reticulum , biochemistry , biology , smooth muscle , nucleotide , gene
Background and purpose: Uridine 5'‐triphosphate (UTP) is a potent vasoconstrictor of cerebral arteries and induces Ca 2+ waves in vascular smooth muscle cells (VSMCs). This study aimed to determine the mechanisms underlying UTP‐induced Ca 2+ waves in VSMCs of the rat basilar artery. Experimental approach: Isometric force and intracellular Ca 2+ ([Ca 2+ ] i ) were measured in endothelium‐denuded rat basilar artery using wire myography and confocal microscopy respectively. Key results: Uridine 5'‐triphosphate (0.1–1000 µmol·L −1 ) concentration‐dependently induced tonic contraction (pEC 50 = 4.34 ± 0.13), associated with sustained repetitive oscillations in [Ca 2+ ] i propagating along the length of the VSMCs as asynchronized Ca 2+ waves. Inhibition of Ca 2+ reuptake in sarcoplasmic reticulum (SR) by cyclopiazonic acid abolished the Ca 2+ waves and resulted in a dramatic drop in tonic contraction. Nifedipine reduced the frequency of Ca 2+ waves by 40% and tonic contraction by 52%, and the nifedipine‐insensitive component was abolished by SKF‐96365, an inhibitor of receptor‐ and store‐operated channels, and KB‐R7943, an inhibitor of reverse‐mode Na + /Ca 2+ exchange. Ongoing Ca 2+ waves and tonic contraction were also abolished after blockade of inositol‐1,4,5‐triphosphate‐sensitive receptors by 2‐aminoethoxydiphenylborate, but not by high concentrations of ryanodine or tetracaine. However, depletion of ryanodine‐sensitive SR Ca 2+ stores prior to UTP stimulation prevented Ca 2+ waves. Conclusions and implications: Uridine 5'‐triphosphate‐induced Ca 2+ waves may underlie tonic contraction and appear to be produced by repetitive cycles of regenerative Ca 2+ release from the SR through inositol‐1,4,5‐triphosphate‐sensitive receptors. Maintenance of Ca 2+ waves requires SR Ca 2+ reuptake from Ca 2+ entry across the plasma membrane via L‐type Ca 2+ channels, receptor‐ and store‐operated channels, and reverse‐mode Na + /Ca 2+ exchange. Mandarin translation of abstract