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Intravascular Pressure Augments Cerebral Arterial Constriction by Inducing Voltage‐Insensitive Ca2+ Waves
Author(s) -
Mufti Rania E.,
Brett Suzanne E.,
Tran Cam Ha,
ElRahman Rasha Abd,
Anfinogenova Yana,
ElYazbi Ahmed,
Cole William C.,
Jones Peter P.,
Chen Wayne SW,
Welsh Donald G.
Publication year - 2011
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.25.1_supplement.1024.5
Subject(s) - myogenic contraction , phosphorylation , myosin light chain phosphatase , chemistry , biophysics , thapsigargin , myosin light chain kinase , ryanodine receptor , medicine , extracellular , endoplasmic reticulum , biology , biochemistry , smooth muscle
This study examined whether elevated intravascular pressure stimulates asynchronous Ca 2+ waves and if their generation contributes to myogenic tone development. Rat cerebral arteries were mounted in an arteriograph, pressurized (20–100 mmHg) and examined under a variety of experimental conditions. Diameter and membrane potential (V M ) were monitored using conventional techniques; Ca 2+ wave generation and myosin light chain (MLC 20 )/MYPT1 phosphorylation were assessed by confocal microscopy and western blot analysis, respectively. Elevating intravascular pressure increased the proportion of smooth muscle cells firing Ca 2+ waves as well as event frequency. Ca 2+ wave augmentation occurred primarily at lower intravascular pressures and ryanodine, an agent that depletes the sarcoplasmic reticulum (SR), eliminated these events. Ca 2+ wave generation was voltage‐insensitive as Ca 2+ channel blockade and perturbations in extracellular [K + ] had little effect on measured parameters. Ryanodine‐induced inhibition of Ca 2+ waves attenuated myogenic tone and MLC 20 phosphorylation without altering arterial V M . Thapsigargin also attenuated Ca 2+ waves, pressure‐induced constriction and MLC 20 phosphorylation. The SR‐driven component of the myogenic response was proportionally greater at lower intravascular pressures and subsequent MYPT1 phosphorylation measures revealed that SR Ca 2+ waves facilitate pressure‐induced MLC 20 phosphorylation through mechanisms that include myosin light chain phosphatase inhibition. Our findings show that mechanical stimuli augment Ca 2+ wave generation and that these transient events facilitate tone development particularly at lower intravascular pressures by providing a proportion of the Ca 2+ required to directly control MLC 20 phosphorylation.