A mathematical model of plasma membrane electrophysiology and calcium dynamics in vascular endothelial cells

• Published in: American Journal of Physiology: Cell Physiology 2007-07, Vol.293 (1), p.C277-C293
• Main Authors: Silva, Haroldo S, Kapela, Adam, Tsoukias, Nikolaos M
• Format: Article
• Language: English
• Subjects: Animals; Arterioles - metabolism; Arterioles - physiology; Calcium; Calcium Signaling - drug effects; Cell Size; Cells; Chloride Channels - metabolism; Computer Simulation; Electrophysiology - methods; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Endothelial Cells - physiology; Ion Channels - agonists; Ion Channels - metabolism; Mathematical models; Membrane Potentials; Membrane Transport Modulators - pharmacology; Membranes; Mesentery - blood supply; Models, Cardiovascular; Muscle, Smooth, Vascular - metabolism; Muscle, Smooth, Vascular - physiology; Plasma; Plasma Membrane Calcium-Transporting ATPases - metabolism; Potassium - metabolism; Potassium Channels, Calcium-Activated - metabolism; Rats; Reproducibility of Results; Sarcolemma - drug effects; Sarcolemma - metabolism; Sarcolemma - physiology; Sarcoplasmic Reticulum Calcium-Transporting ATPases - metabolism; Sodium Channels - metabolism; Veins & arteries; Voltage-Dependent Anion Channels - metabolism
• ISSN: 0363-6143; 1522-1563
• DOI: 10.1152/ajpcell.00542.2006

Department of Biomedical Engineering, Florida International University, Miami, Florida Submitted 22 October 2006 ; accepted in final form 20 March 2007 Vascular endothelial cells (ECs) modulate smooth muscle cell (SMC) contractility, assisting in vascular tone regulation. Cytosolic Ca 2+ concentration ([Ca 2+ ] i ) and membrane potential ( V m ) play important roles in this process by controlling EC-dependent vasoactive signals and intercellular communication. The present mathematical model integrates plasmalemma electrophysiology and Ca 2+ dynamics to investigate EC responses to different stimuli and the controversial relationship between [Ca 2+ ] i and V m . The model contains descriptions for the intracellular balance of major ionic species and the release of Ca 2+ from intracellular stores. It also expands previous formulations by including more detailed transmembrane current descriptions. The model reproduces V m responses to volume-regulated anion channel (VRAC) blockers and extracellular K + concentration ([K + ] o ) challenges, predicting 1 ) that V m changes upon VRAC blockade are [K + ] o dependent and 2 ) a biphasic response of V m to increasing [K + ] o . Simulations of agonist-induced Ca 2+ mobilization replicate experiments under control and V m hyperpolarization blockade conditions. They show that peak [Ca 2+ ] i is governed by store Ca 2+ release while Ca 2+ influx (and consequently V m ) impacts more the resting and plateau [Ca 2+ ] i . The V m sensitivity of rest and plateau [Ca 2+ ] i is dictated by a [Ca 2+ ] i "buffering" system capable of masking the V m -dependent transmembrane Ca 2+ influx. The model predicts plasma membrane Ca 2+ -ATPase and Ca 2+ permeability as main players in this process. The heterogeneous V m impact on [Ca 2+ ] i may elucidate conflicting reports on how V m influences EC Ca 2+ . The present study forms the basis for the development of multicellular EC-SMC models that can assist in understanding vascular autoregulation in health and disease. microcirculation; vascular tone regulation; calcium influx pathway(s), plasma membrane Ca 2+ -ATPase Address for reprint requests and other correspondence: N. M. Tsoukias, Dept. of Biomedical Engineering, Florida International Univ., 10555 W. Flagler St., TEC 2674, Miami, FL 33174 (e-mail: tsoukias{at}fiu.edu )