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Role of localized calcium events in regulation of vascular tone: A theoretical investigation
Author(s) -
Parikh Jaimit,
Kapela Adam,
Tsoukias Nikolaos M
Publication year - 2013
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.27.1_supplement.678.9
Subject(s) - biophysics , chemistry , calcium , voltage dependent calcium channel , membrane potential , calcium signaling , t type calcium channel , electrophysiology , potassium channel , gating , neuroscience , trpv4 , ion channel , calcium activated potassium channel , vascular smooth muscle , bk channel , sodium channel , vascular tone , receptor , biology , sodium , endocrinology , smooth muscle , biochemistry , organic chemistry , nitric oxide
Localized calcium (Ca 2+ ) events like sparks, puffs, pulsars and sparklets have been identified in the vascular cells. They have been suggested to play an important role in modulation of vessel tone. Theoretical modeling can provide quantitative insights and improve the fundamental understanding of the generation of these localized Ca 2+ events. Hence we develop detailed finite element cellular models of Ca 2+ dynamics and membrane electrophysiology in smooth muscle and endothelial cells. These models are integrated and modified to include myoendothelial projections with localized IP 3 receptors, intermediate conductance Ca 2+ activated potassium channels (IK Ca ) and TRPV4 channels. Activation of TRPV4 channels resulted in localized Ca 2+ signals (sparklets). A single TRPV4 channel activation in absence of other channels and pumps resulted in localized calcium increase >;100nM and a spatial spread of ~ 6μm. The parameters of sparklets are affected by variety of factors of which open time of the channel, cooperative gating of the channels, diffusion coefficient of calcium and channel current can be the most important. The localized Ca 2+ increase can activate IK Ca channels and cause endothelium‐derived hyperpolarizing response modulating the vascular tone. The study provides a novel theoretical tool to examine the mechanisms behind localized calcium events and the regulation of vascular tone. (Supported by NIH SC1HL95101).