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Effect of Altered Membranous Architecture in Vascular Smooth Muscle Contractility
Author(s) -
Kuo KuoHsing
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.lb20
Subject(s) - contractility , vascular smooth muscle , endoplasmic reticulum , biophysics , agonist , chemistry , phenylephrine , receptor , intracellular , medicine , microbiology and biotechnology , endocrinology , biology , biochemistry , smooth muscle , blood pressure
Vascular smooth muscle is the direct effector on contractility of blood vessels and is pivotal in maintaining hemodynamic stability. In response to agonist stimulations, such as neurotransmitters, hormones or drugs, the smooth muscle cell (SMC) contracts in close correspondence to the local fluctuations of intracellular calcium ions (Ca2+), which is accomplished by a sequence of repetitive Ca2+ cycling events till the agonist is removed. In brief, the Ca2+ cycles are initiated by receptors binding on the plasma membrane (PM) and followed by: (1) Ca2+ release from the sarcoplasmic reticulum (SR) to activate the contractile machinery, (2) Ca2+ entering through the PM to refill SR Ca2+ storage and (3) Ca2+ removal from the cytosol, all underly the mechanisms of local and wave‐like Ca2+ transient signals. The membranous microarchitecture and microdomain, flanked by the PM and peripheral SR, are the gates to Ca2+ entry/removal and regulate Ca2+ signals. Altered PM may compromise the encoding of the Ca2+ signal and further affect SMC contractility. The objective of this study is to investigate the functional role of the membranous microarchitecture, the caveolar domain in specific, during adrenergic stimulation. The denuded venous vascular smooth muscle was incubated with the cholesterol depleting agent, methyl‐B‐cyclodextrin (MCD), to disrupt the caveolar domain to assess the impact of the altered PM on phenylephrine (PE)‐induced contractility. We observed enhanced sensitivity to PE and a right shift of the dose‐response curve for force generation in the MCD‐treated SMC. Ultrastructurally, the MCD‐treated SMC were characterized by a wavy PM, lack of caveolar domains and enlarged peripheral SR. Notably, the frequency of the wave‐like transient Ca2+ was also enhanced by a dose‐dependent feature to PE concentrations. We believe that the intensified frequency of the wave‐like Ca2+ signal underlies the enhanced PE sensitivity in MCD‐treated SMC and disrupted caveolar domains may delay Ca2+ removal and augment SR Ca2+ retention, contributing to the intensified frequency of the Ca2+ signals. Support or Funding Information The Discovery Grant by The Natural Sciences and Engineering Research Council of Canada (NSERC)