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

Silva, Haroldo S; Kapela, Adam; Tsoukias, Nikolaos M.

doi:10.1152/ajpcell.00542.2006

Cited by 72 publications

(114 citation statements)

References 86 publications

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“…Our laboratory has previously developed detailed mathematical models of plasma membrane electrophysiology and Ca 2ϩ dynamics in isolated EC (44) and SMC (28). Schematics of these models are depicted in Fig.…”

Section: Methodsmentioning

confidence: 99%

A mathematical model of vasoreactivity in rat mesenteric arterioles. II. Conducted vasoreactivity

Kapela

Nagaraja

Tsoukias

2010

American Journal of Physiology-Heart and Circulatory Physiology

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concentration in neighboring ECs. The small endothelial Ca 2ϩ spread can amplify the total current generated at the local site by the ECs and through the nitric oxide pathway, by the SMCs, and thus reduces the number of stimulated cells required to induce distant responses. The distance of the electrotonic and Ca 2ϩ spread depends on the magnitude of SM prestimulation and the number of SM layers. Model results are consistent with experimental data for vasoreactivity in rat mesenteric resistance arteries. intercellular communication; membrane potential; calcium dynamics FOCAL APPLICATION OF CERTAIN vasoactive agents to microvessels may cause significant vasomotor responses, both locally and at relatively distant sites. The distant responses are mediated by intrinsic signal transduction mechanisms within the vascular wall, independent of the diffusion of the stimulating agent, hemodynamic effects, or innervations. These conducted responses have been reported in different vascular beds and species (12,14,20,33,41) and may play a role in both the rapid and long-term coordination of microvascular function. Vasodilatation initiated locally by increased metabolic demand may be conducted upstream to feed arteries to allow adequate increase in blood flow (42, 43); conducted vasoconstriction may be important in the tubuloglomerular feedback mechanism of renal autoregulation (20); and theoretical simulations suggest that axial communication in the vasculature is required to suppress the generation of large proximal shunts during longterm structural adaptation of microvascular networks (38).The underlying mechanisms of spreading responses remain poorly understood, but electrotonic transmission of membrane potential changes (⌬V m ) and calcium (Ca 2ϩ ) waves through the endothelium seem to play the major role (46, 48). In some vessels, including in rat mesenteric resistance arteries (RMA), the signal is attenuated away from the stimulus site, and the vasoreactivity observed at a distant site is attributed to Ca 2ϩ -independent passive electronic diffusion through gap junctions (20,47). In other vascular beds, the conducted signal can spread over significant distances with minimal attenuation, and thus facilitating/regenerative mechanisms should be involved (24). A number of hypotheses have been proposed to account for the facilitation of the transmitted signal. One suggestion is that membrane hyperpolarization is enhanced by inwardly rectifying potassium (K ir ) channels and/or the sodium-potassium (NaK) pump (8). Alternatively, a wave of nitric oxide (NO) release along the arteriolar endothelium, triggered by a spread of Ca 2ϩ , could induce spreading dilatation (4, 10). Remote Ca 2ϩ waves have been reported in hamster feed arteries (10, 50). A regenerative mechanism based on the activation of endothelial voltage-dependent sodium and calcium channels has also been suggested (16).A number of theoretical studies have been performed to investigate spreading responses. Hirst and Neild (26) modeled a vessel segment as a continuo...

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Section: Methodsmentioning

confidence: 99%

A mathematical model of vasoreactivity in rat mesenteric arterioles. II. Conducted vasoreactivity

Kapela

Nagaraja

Tsoukias

2010

American Journal of Physiology-Heart and Circulatory Physiology

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“…We have previously developed detailed mathematical models of plasma membrane electrophysiology and Ca 2+ dynamics in isolated EC [78] and SMC [56].…”

Section: Methodsmentioning

confidence: 99%

“…We have recently presented a theoretical analysis of myoendothelial communication [129] by integrating an isolated EC [78] and a SMC [56] model shown in and species [130][131][132][133][134] and may play a role in both the rapid and long-term coordination of microvascular function. Vasodilatation initiated locally by increased metabolic demand may be conducted upstream to feed arteries to allow adequate increase in blood flow [135,136]; conducted vasoconstriction may be important in the tubuloglomerular feedback mechanism of renal autoregulation [133]; and theoretical simulations suggest that axial communication in the vasculature is required to suppress the generation of large proximal shunts during long-term structural adaptation of microvascular networks [137].…”

Section: Multicellular Modelingmentioning

confidence: 99%

“…The EC was divided into two compartments representing the bulk EC and the MPs as shown in Figure 1a. arteries by Bychkov et al [180], rescaled using rat mesenteric data and implemented in our EC model [78]. IK Ca are localized in MPs by modifying this parameter as listed in EC ions and IP 3 :…”

Section: Compartmental Modelmentioning

confidence: 99%

“…In our current EC model [78], IP 3 R open probability is described using the probability curve shown in Figure 6.4 cm/s; P KNSC = 1.06·P NaNSC ; P CaNSC = 4.54·P NaNSC ; d NSCmin = 0.0244. ; n Kir = 0.5. …”

Section: Calcium Induced Calcium Release In Ip 3 Receptormentioning

confidence: 99%

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Theoretical Investigations of Communication in the Microcirculation: Conducted Responses, Myoendothelial Projections and Endothelium Derived Hyperpolarizing Factor

Nagaraja¹

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This dissertation, written by Sridevi Nagaraja, and entitled Theoretical investigations of intercellular communication in the microcirculation: conducted responses, myoendothelial projections and endothelium derived hyperpolarizing factor, having been approved in respect to style and intellectual content, is referred to you for judgment.We have read this dissertation and recommend that it be approved. _______________________________________Wei-Chiang Lin dynamics in vascular cells in single as well as multicellular models. Advancement of these models is necessary to achieve the level of sophistication analogous to cardiac models. These models will contribute towards the development of a theoretical framework for the understanding of microcirculatory phenomena. It is also one of the most thoroughly studied vascular beds with vast amount of experimental data available. Therefore, in most of our models we use data from small rat mesenteric arteries (RMAs). This section describes the major channels and pumps present within the cytosol in the longitudinal direction of the cell.Through this process, it has become obvious that detailed models of Ca is still a need to build upon previous modeling work in order to develop cellular models that will assist in the investigations of vascular tone regulation in health and disease. Other channels specific to EC are described below. Inward rectifier potassium channelsInward rectifier potassium channels (K ir ) are sensitive to extracellular concentration of potassium in the range of 1 to 20 mM. These channels increase entry of potassium into the cell thereby hyperpolarizing of EC and subsequently the SMC. They are present in almost all endothelial cells and contribute towards the resting V m of the EC. EC K ir channels are known to be activated not only by potassium but also by shear stress. Theoretical modeling of vascular ECsThe first endothelial cell models were based on earlier generic models of Ca Endothelium derived controllers Nitric oxideNitric oxide was identified as the endothelium derived relaxing factor in 1980 ProstacyclinProstacyclin (PGI2) in rat mesenteric arterioles, PGI2 does not exert a hyperpolarizing effect. The involvement of PGI2 pathways is usually studied using COX inhibitor (Indomethacin). Endothelium derived hyperpolarizing factorEDHF is an endothelium derived non-nitric oxide (NO) and non-cyclicoxygenase and EC hyperpolarization by activation of IK Ca and SK Ca is now a widely accepted finger print of EDHF action across many studies.However, its propagation to the SMC is still being investigated. Myoendothelial feedbackStudies have shown that endothelium derived pathways can also be induced during SMC stimulation which brought about the concept of myoendothelial feedback. where R gj is gap junction resistance, and ∆V gj represents V m cells n-th and m-th ( Figure 2.2). where P gj,S is the gap junction permeability to S (e.g., Ca rectification is low at physiological concentration gradients, and a simpler linear approximation can ...

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Networking in the French‐Speaking Countries and Current Trends in International Assistance

Menou¹

1998

Bul. Am. Soc. Info. Sci. Tech.

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

Cited by 72 publications

References 86 publications

A mathematical model of vasoreactivity in rat mesenteric arterioles. II. Conducted vasoreactivity

A mathematical model of vasoreactivity in rat mesenteric arterioles. II. Conducted vasoreactivity

Theoretical Investigations of Communication in the Microcirculation: Conducted Responses, Myoendothelial Projections and Endothelium Derived Hyperpolarizing Factor

Networking in the French‐Speaking Countries and Current Trends in International Assistance

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