A New Muscle Activation Dynamics Model, That Simulates the Calcium Kinetics and Incorporates the Role of Store-Operated Calcium Entry Channels, to Enhance the EMG-Driven Hill-type Models

Author(s):  
Moemen Hussein ◽  
Said Shebl ◽  
Rehab Elnemr ◽  
Hesham Elkaranshawy

Abstract Hill-type models are frequently used in biomechanical simulations. They are attractive for their low computational cost and close relation to commonly measured musculotendon parameters. Still, more attention is needed to improve the activation dynamics of the model specifically because of the nonlinearity observed in the EMG-Force relation. Moreover, one of the important and practical questions regarding the assessment of the model's performance is how adequately can the model simulate any fundamental type of human movement without modifying model parameters for different tasks? This paper tries to answer this question by proposing a simple physiologically based activation dynamics model. The model describes the ?kinetics of the calcium dynamics while activating and deactivating the muscle contraction process. Hence, it allowed simulating the recently discovered role of store-operated calcium entry (SOCE) channels as immediate counter-flux to calcium loss across the tubular system during excitation-contraction coupling. By comparing the ability to fit experimental data without readjusting the parameters, the proposed model has proven to have more steady performance than phenomenologically based models through different submaximal isometric contraction levels. This model indicates that more physiological insights is key for improving Hill-type model performance.

2015 ◽  
Vol 65 (10) ◽  
pp. A902
Author(s):  
Senthil Selvaraj ◽  
Brij Singh ◽  
Christian Bollensdorff ◽  
Jassim Al Suwaidi ◽  
Magdi Yacoub

2019 ◽  
Vol 116 (3) ◽  
pp. 237a-238a
Author(s):  
Savannah J. West ◽  
Qiaochu Wang ◽  
Michael X. Zhu ◽  
Askar M. Akimzhanov ◽  
Darren Boehning

Author(s):  
Francisco Javier Martín-Romero ◽  
Aida M. López-Guerrero ◽  
Ignacio S. Álvarez ◽  
Eulalia Pozo-Guisado

2002 ◽  
Vol 157 (7) ◽  
pp. 1267-1278 ◽  
Author(s):  
Donna L. Cioffi ◽  
Timothy M. Moore ◽  
Jerry Schaack ◽  
Judy R. Creighton ◽  
Dermot M.F. Cooper ◽  
...  

Acute transitions in cytosolic calcium ([Ca2+]i) through store-operated calcium entry channels catalyze interendothelial cell gap formation that increases permeability. However, the rise in [Ca2+]i only disrupts barrier function in the absence of a rise in cAMP. Discovery that type 6 adenylyl cyclase (AC6; EC 4.6.6.1) is inhibited by calcium entry through store-operated calcium entry pathways provided a plausible explanation for how inflammatory [Ca2+]i mediators may decrease cAMP necessary for endothelial cell gap formation. [Ca2+]i mediators only modestly decrease global cAMP concentrations and thus, to date, the physiological role of AC6 is unresolved. Present studies used an adenoviral construct that expresses the calcium-stimulated AC8 to convert normal calcium inhibition into stimulation of cAMP, within physiologically relevant concentration ranges. Thrombin stimulated a dose-dependent [Ca2+]i rise in both pulmonary artery (PAECs) and microvascular (PMVEC) endothelial cells, and promoted intercellular gap formation in both cell types. In PAECs, gap formation was progressive over 2 h, whereas in PMVECs, gap formation was rapid (within 10 min) and gaps resealed within 2 h. Expression of AC8 resulted in a modest calcium stimulation of cAMP, which virtually abolished thrombin-induced gap formation in PMVECs. Findings provide the first direct evidence that calcium inhibition of AC6 is essential for endothelial gap formation.


2021 ◽  
Vol 12 ◽  
Author(s):  
Benedito M. Santos ◽  
Bárbara K. M. Dias ◽  
Myna Nakabashi ◽  
Celia R. S. Garcia

Previously we have reported that the G protein-coupled receptor (GPCR)-like PfSR25 in Plasmodium falciparum is a potassium (K+) sensor linked to intracellular calcium signaling and that knockout parasites (PfSR25-) are more susceptible to oxidative stress and antimalarial compounds. Here, we explore the potential role of PfSR25 in susceptibility to the antimalarial compounds atovaquone, chloroquine, dihydroartemisinin, lumefantrine, mefloquine, piperaquine, primaquine, and pyrimethamine and the Medicine for Malaria Venture (MMV) compounds previously described to act on egress/invasion (MMV006429, MMV396715, MMV019127, MMV665874, MMV665878, MMV665785, and MMV66583) through comparative assays with PfSR25- and 3D7 parasite strains, using flow cytometry assays. The IC50 and IC90 results show that lumefantrine and piperaquine have greater activity on the PfSR25- parasite strain when compared to 3D7. For MMV compounds, we found no differences between the strains except for the compound MMV665831, which we used to investigate the store-operated calcium entry (SOCE) mechanism. The results suggest that PfSR25 may be involved in the mechanism of action of the antimalarials lumefantrine and piperaquine. Our data clearly show that MMV665831 does not affect calcium entry in parasites after we depleted their internal calcium pools with thapsigargin. The results demonstrated here shed light on new possibilities on the antimalarial mechanism, bringing evidence of the involvement of the GPCR-like PfSR25.


Author(s):  
Kaori Murata ◽  
Takao Morita ◽  
Akihiro Nezu ◽  
Masato Saitoh ◽  
Akihiko Tanimura

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