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Transient myogenic response provides insight to mechanotransductive pathways in vascular smooth muscle cells
Author(s) -
Carlson Brian E.,
Haydar Nada,
Beard Daniel A.
Publication year - 2012
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.26.1_supplement.853.1
Subject(s) - myogenic contraction , vascular smooth muscle , biophysics , cytosol , steady state (chemistry) , transient response , transient (computer programming) , chemistry , electrophysiology , smooth muscle , anatomy , biology , neuroscience , biochemistry , computer science , engineering , endocrinology , enzyme , electrical engineering , operating system
The myogenic response, where vessels in the microvasculature can exhibit steady state constriction with an increase in intraluminal pressure, is facilitated through transduction of stress by vascular smooth muscle (VSM) cells. Traditionally the myogenic response has been quantified by recording steady‐state vessel diameters as a function of intraluminal pressure in isolated vessels. However this steady‐state response of vessel diameter provides less information than the complete transient response during these experiments. Our approach here utilizes transient response data of microvessels as they progress to steady state to uncover plausible mechanotransductive pathways. We have constructed a computational model considering vessel wall mechanics, VSM force generation and VSM Ca 2+ handling and electrophysiology that is able to generate this transient myogenic response and we compare these simulations to transient response data from the literature. Through this comparison we can show that direct strain activation of ion channels (possibly non‐selective cation and/or L‐type Ca 2+ channels) are likely responsible for the initial increase in cytosolic Ca 2+ however slower mechanotransductive pathways (possibly mediated by cytochrome P‐450) must be present to explain the longer timescale transients in both cytosolic Ca 2+ and vessel diameter observed experimentally. Supported by NSF CBET 1133260.