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

Am J Physiol Cell Physiol. 2007 Jul;293(1):C277-93. doi: 10.1152/ajpcell.00542.2006. Epub 2007 Apr 25.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arterioles / metabolism
  • Arterioles / physiology
  • Calcium Signaling* / drug effects
  • Cell Size
  • Chloride Channels / metabolism
  • Computer Simulation
  • Electrophysiology / methods*
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Endothelial Cells / physiology*
  • Ion Channels / agonists
  • Ion Channels / metabolism*
  • Membrane Potentials
  • Membrane Transport Modulators / pharmacology
  • Mesentery / blood supply*
  • Models, Cardiovascular*
  • Muscle, Smooth, Vascular / metabolism
  • Muscle, Smooth, Vascular / physiology
  • 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
  • Voltage-Dependent Anion Channels / metabolism


  • Chloride Channels
  • Ion Channels
  • Membrane Transport Modulators
  • Potassium Channels, Calcium-Activated
  • Sodium Channels
  • Voltage-Dependent Anion Channels
  • Plasma Membrane Calcium-Transporting ATPases
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases
  • Potassium