Analysis of decay kinetics of the cytosolic calcium transient induced by oxytocin in rat myometrium smooth muscle cells

Karakhim, S. O.; Шлыков, С. Г.; Babich, L. G.; Sinko, D V

doi:10.1007/s10974-021-09598-7

Cited by 3 publications

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References 43 publications

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“…As can be seen from Table 1, the model includes about thirty variables, the values of most of which may vary over a wide range, depending on the studied smooth muscle tissue, and for some (such as reaction rate constants) the experimental values in general are unknown. However, as a result of studies, two characteristic features of the model behavior were found, which can be briefly called a single cytosolic Ca 2+ transient mode [37, 50] and an oscillatory mode [37, 51]. Any ratios of the variables always lead to one or the other mode (at least, we have not discovered any other modes).…”

Section: Study Of a Model Of Calcium-induced Calcium Release In A Smo...mentioning

confidence: 78%

A model of calcium-induced calcium release from the sarcoplasmic reticulum in the smooth muscle cell and its investigation by mathematical modeling

Zhuk

Karakhim

Костерін

2023

Preprint

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A model of calcium-induced calcium release (CICR) from the sarcoplasmic reticulum was developed, simulating the behavior of the smooth muscle cell under conditions of its agonist stimulation. The mathematical model is a system of thirteen differential equations. In the initial (basal) state, the parameters of active and passive transport of Ca2+ through both the plasma membrane and the sarcoplasmic reticulum membrane are adjusted. A study of the model showed that, depending on the model parameters, the cell system can demonstrate two types of calcium concentration changes in the cytosol: a single Ca2+ transient and an oscillatory mode. After stimulation is completed, the cell system returns to the basal state (under in vivo conditions) or goes to a new steady-state level (under in vitro conditions), except when the cell system is in oscillatory mode. It is shown that the sarcoplasmic reticulum can act both as a passive participant in the process of Ca2+ accumulation in the smooth muscle cell, acting as a buffer, and play a major role in this process by significantly increasing the Ca2+ concentration in the cytosol, which is initiated by Ca2+ entry from the extracellular space. It was found that after stimulation of the smooth muscle cell, the net Ca2+ flux from the cytosol increases due to an increase in Ca2+ concentration in the cytosol, while the net Ca2+ flux into the cytosol first increases due to an increase in the number of open calcium channels located on the membrane of the sarcoplasmic reticulum. It then begins to decrease due to a decrease in the Ca2+ concentration gradient across the membrane of the sarcoplasmic reticulum. Therefore, at a certain time point these fluxes become equal and the process of Ca2+ accumulation in the cytosol is terminated. Thus, calcium-induced calcium release is terminated spontaneously, resulting in the formation of a single cytosolic Ca2+ transient. As a result of calcium-induced calcium release, the sarcoplasmic reticulum is not completely emptied, but retains quite significant amounts of Ca2+. The possibility of Ca2+ redistribution between the three compartments (extracellular space, cytosol and sarcoplasmic reticulum) creates the possibility of oscillation of cytosolic Ca2+ concentration. The oscillation amplitude and frequency can remain practically unchanged for a considerable period. The developed model qualitatively reproduces the results of experimental studies conducted to identify store-operated calcium channels using the inhibitors of the calcium pump of the sarcoplasmic reticulum in a calcium-free medium.

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Section: Study Of a Model Of Calcium-induced Calcium Release In A Smo...mentioning

confidence: 78%

A model of calcium-induced calcium release from the sarcoplasmic reticulum in the smooth muscle cell and its investigation by mathematical modeling

Zhuk

Karakhim

Костерін

2023

Preprint

Self Cite

View full text Add to dashboard Cite

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“…Thus, the chronic intake of TiO 2 nanomaterial is accompanied by a significant inhibition of the contractile function of the gastric SMs. Since the parameters of the contraction and relaxation phases do not differ by the magnitude of the inhibitory effects, it can be assumed that TiO 2 effects are not specific for particular Ca 2+ systems that participate in the generation of contractile responses (Taggart et al, 1997;Karakhim et al, 2021).…”

Section: Resultsmentioning

confidence: 99%

Mechanokinetics of the spontaneous contractions of smooth muscles in the stomach and large intestine of rats under chronic effect of ТiО2 nanoparticles

et al. 2023

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Background. Currently, nano-sized materials of titanium dioxide (TiО2) have wide industrial uses, particularly in the food industry and pharmacology. Therefore, the problem of TiО2 toxicity to living organisms in case of their chronic in vivo intake needs thorough investigation. As nanoparticles enter the internal environment of the body, they spread with the bloodstream to tissues and organs, where they partially accumulate. Thus studying the state of the pacemaker mechanisms of regulation of smooth muscle spontaneous contractions in the stomach and large intestine under chronic exposure to TiО2 nanoparticles is relevant and interesting. The purpose of this research work was to study the spontaneous contractile activity of the gastric and large intestine smooth muscles of rats under chronic (for 6 months) intake of an aqueous suspension of TiО2 nanoparticles. Materials and Methods. Wistar rats were used in the experiments. Rats of the experimental group were daily intragastrically administered an aqueous suspension of ТіО2 nanoparticles for six months at a dose of 0.1 mg/kg. The study of the mechanokinetics of the contraction-relaxation process of muscle preparations was carried out according to the method (Kosterin et al., 2021) with the calculation of the mechanokinetic parameters of the contraction-relaxation cycle: force (Fmax, FC and FR), time (τ0, τC and τR), impulse (Іmax, ІC and ІR) and velocity (VC and VR). Results. A comprehensive mechanokinetic analysis of spontaneous contractions of the antrum and caecum circular smooth muscles was carried out in control and under chronic in vivo exposure to ТіО2 nanocolloids (0.1 mg/kg/day) for 6 months. It was found that the chronic action of ТіО2 nanocolloids significantly inhibits the contractile activity of the antrum smooth muscles accompanied by a decrease in all mechanokinetic parameters of time, force, velocity and impulse. Under the same conditions, inhibition of the spontaneous contractions of the large intestine smooth muscles was observed. However, the time (τ0, τC and τR) and impulse (Іmax, ІC and ІR) parameters increased for these muscles against the background of the decrease in the force and velocity mechanokinetic parameters. Conclusions. Modulation of the mechanokinetic parameters of the spontaneous contractile activity of the stomach and large intestine smooth muscles of rats under chronic intragastric administration of ТіО2 nanocolloids suggests that the functioning of pacemakers changes significantly under these conditions. Since the parameters of the contraction and relaxation phases of both the stomach and the large intestine smooth muscles do not differ by the magnitude of the inhibitory effects, it can be assumed that the effects of ТіО2 are not specific for particular Са2+ transport systems involved in contractile responses.

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Sulfation and Its Effect on the Bioactivity of Magnolol, the Main Active Ingredient of Magnolia Officinalis

Xie

Gan

et al. 2022

Metabolites

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Magnolol, the main active ingredient of Magnolia officinalis, has been reported to display anti-inflammatory activity. Sulfation plays an important role in the metabolism of magnolol. The magnolol sulfated metabolite was identified by the ultra-performance liquid chromatography to quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and a proton nuclear magnetic resonance (1H-NMR). The magnolol sulfation activity of seven major recombinant sulfotransferases (SULTs) isoforms (SULT1A1*1, SULT1A1*2, SULT1A2, SULT1A3, SULT1B1, SULT1E1, and SULT2A1) was analyzed. The metabolic profile of magnolol was investigated in liver S9 fractions from human (HLS9), rat (RLS9), and mouse (MLS9). The anti-inflammatory effects of magnolol and its sulfated metabolite were evaluated in RAW264.7 cells stimulated by lipopolysaccharide (LPS). Magnolol was metabolized into a mono-sulfated metabolite by SULTs. Of the seven recombinant SULT isoforms examined, SULT1B1 exhibited the highest magnolol sulfation activity. In liver S9 fractions from different species, the CLint value of magnolol sulfation in HLS9 (0.96 µL/min/mg) was similar to that in RLS9 (0.99 µL/min/mg) but significantly higher than that in MLS9 (0.30 µL/min/mg). Magnolol and its sulfated metabolite both significantly downregulated the production of inflammatory mediators (IL-1β, IL-6 and TNF-α) stimulated by LPS (p < 0.001). These results indicated that SULT1B1 was the major enzyme responsible for the sulfation of magnolol and that the magnolol sulfated metabolite exhibited potential anti-inflammatory effects.

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Analysis of decay kinetics of the cytosolic calcium transient induced by oxytocin in rat myometrium smooth muscle cells

Cited by 3 publications

References 43 publications

A model of calcium-induced calcium release from the sarcoplasmic reticulum in the smooth muscle cell and its investigation by mathematical modeling

A model of calcium-induced calcium release from the sarcoplasmic reticulum in the smooth muscle cell and its investigation by mathematical modeling

Mechanokinetics of the spontaneous contractions of smooth muscles in the stomach and large intestine of rats under chronic effect of ТiО2 nanoparticles

Sulfation and Its Effect on the Bioactivity of Magnolol, the Main Active Ingredient of Magnolia Officinalis

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