A mathematical model of Ca2+ dynamics in rat mesenteric smooth muscle cell: Agonist and NO stimulation

Adam Kapela, Anastasios Bezerianos, Nikolaos M. Tsoukias

Research output: Contribution to journalArticle

Abstract

A mathematical model of calcium dynamics in vascular smooth muscle cell (SMC) was developed based on data mostly from rat mesenteric arterioles. The model focuses on (a) the plasma membrane electrophysiology; (b) Ca2+ uptake and release from the sarcoplasmic reticulum (SR); (c) cytosolic balance of Ca2+, Na+, K+, and Cl- ions; and (d) IP3 and cGMP formation in response to norepinephrine (NE) and nitric oxide (NO) stimulation. Stimulation with NE induced membrane depolarization and an intracellular Ca2+ ([Ca2+]i) transient followed by a plateau. The plateau concentrations were mostly determined by the activation of voltage-operated Ca2+ channels. NE causes a greater increase in [Ca2+]i than stimulation with KCl to equivalent depolarization. Model simulations suggest that the effect of [Na+]i accumulation on the Na+/Ca2+ exchanger (NCX) can potentially account for this difference. Elevation of [Ca2+]i within a concentration window (150-300 nM) by NE or KCl initiated [Ca2+]i oscillations with a concentration-dependent period. The oscillations were generated by the nonlinear dynamics of Ca2+ release and refilling in the SR. NO repolarized the NE-stimulated SMC and restored low [Ca2+]i mainly through its effect on Ca2+-activated K+ channels. Under certain conditions, Na+-K+-ATPase inhibition can result in the elevation of [Na+]i and the reversal of NCX, increasing resting cytosolic and SR Ca2+ content, as well as reactivity to NE. Blockade of the NCX's reverse mode could eliminate these effects. We conclude that the integration of the selected cellular components yields a mathematical model that reproduces, satisfactorily, some of the established features of SMC physiology. Simulations suggest a potential role of intracellular Na+ in modulating Ca2+ dynamics and provide insights into the mechanisms of SMC constriction, relaxation, and the phenomenon of vasomotion. The model will provide the basis for the development of multi-cellular mathematical models that will investigate microcirculatory function in health and disease.

Original languageEnglish (US)
Pages (from-to)238-260
Number of pages23
JournalJournal of Theoretical Biology
Volume253
Issue number2
DOIs
StatePublished - Jul 21 2008
Externally publishedYes

Fingerprint

Norepinephrine
Smooth muscle Cells
Nitric Oxide
Nitric oxide
smooth muscle
myocytes
agonists
Smooth Muscle Myocytes
nitric oxide
Muscle
Rats
Theoretical Models
mathematical models
Cells
Mathematical Model
Mathematical models
calcium
rats
Sarcoplasmic Reticulum
norepinephrine

Keywords

  • Ion channels
  • Membrane potential
  • Microcirculation
  • Vascular tone

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Medicine(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Modeling and Simulation
  • Statistics and Probability
  • Applied Mathematics

Cite this

A mathematical model of Ca2+ dynamics in rat mesenteric smooth muscle cell : Agonist and NO stimulation. / Kapela, Adam; Bezerianos, Anastasios; Tsoukias, Nikolaos M.

In: Journal of Theoretical Biology, Vol. 253, No. 2, 21.07.2008, p. 238-260.

Research output: Contribution to journalArticle

Kapela, Adam ; Bezerianos, Anastasios ; Tsoukias, Nikolaos M. / A mathematical model of Ca2+ dynamics in rat mesenteric smooth muscle cell : Agonist and NO stimulation. In: Journal of Theoretical Biology. 2008 ; Vol. 253, No. 2. pp. 238-260.
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