Premium
A mathematical model of plasma membrane electrophysiology and calcium dynamics in rat mesenteric endothelial cells
Author(s) -
Silva Haroldo Souza,
Kapela Adam,
Tsoukias Nikolaos
Publication year - 2006
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.20.4.a410
Subject(s) - electrophysiology , dynamics (music) , biophysics , chemistry , calcium , membrane , neuroscience , biology , biochemistry , physics , organic chemistry , acoustics
Endothelial cells (ECs) play a key role in vascular tone modulation by regulating adjacent smooth muscle cell (SMC) contraction in blood vessel walls. Calcium (Ca 2+ ) has a major role in EC functionality, including production of vasoactive substances such as nitric oxide (NO). However, influence of transmembrane potential (Vm) on EC Ca 2+ remains controversial. Thus, understanding EC Ca 2+ dynamics is indispensable for unlocking vascular tone regulation pathways. The model integrates both EC Ca 2+ dynamics and plasmalemmal electrical activity to investigate EC responses to various stimulatory conditions and the interdependency of Ca 2+ and Vm. The model, unlike previous modeling efforts, contains a detailed description of plasma membrane electrophysiology. It also includes intracellular Ca 2+ handling components and Ca 2+ ‐dependent NO production. Most model components were found based on recent EC experimental data or adapted from previous EC models. The model reproduces experimentally observed EC Vm responses to volume‐sensitive anion channel inhibitors and to extracellular potassium concentration changes. In addition, simulated Ca 2+ transients during agonist stimulation agree qualitatively with experimental data, both under control and Ca 2+ ‐activated potassium channel blockade conditions. Model also simulates agonist‐induced NO transients in ECs as observed in the literature. Simulations predict volume‐sensitive channels as major determinants of resting Vm, and Ca 2+ transient profiles being modulated but not determined by Vm. The EC model can assist in the study of SMC‐EC interactions and help understand whole vessel autoregulation, both in health and disease. Supported by AHA grant NSDG043506N and Ronald E. McNair Postbaccalaureate Achievement Program.