Thermomechanokinetics of viscoelastic deformation of smooth muscles in the rat gastrointestinal tract. II. Thermomechanokinetics of hysteresis of stomach and large intestine smooth muscles

Tsymbalyuk, O. V.; Костерін, С. О.

doi:10.30970/sbi.0603.214

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“…As the previous biochemical studies had decisively proven that calix [4]arene С-90 has selective influence on the systems of primary active transport of Са 2+ into uterine SMC (first and foremost, due to PMCA inhibition) [4,22,23], our further studies were related to the mechanokinetic analysis of relaxation processes of spontaneous phase contractions of the myometrium preparations. The relaxation process in visceral SM is accompanied by a reduction in the intracellular concentration of Са 2+ ions in the myoplasm [7,10,17,[19][20][21]. On the background of all the applied concentrations (10 -7 -10 -4 М), calix [4]arene С-90 conditioned the slowing down of the relaxation of spontaneous contractions in uterine muscle preparations of rats, which was reflected in a reliable decrease in the parameter for the maximal velocity of the relaxation phase (V R ) (Fig.…”

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confidence: 99%

Modulating the mechanokinetics of spontaneous contractions of the myometrium of rats using calix[4]arene C-90 – plasma membrane calcium ATPase inhibitor

Tsymbalyuk¹

2021

Biol. Stud.

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Introduction. Plasma membrane calcium ATPase is a constitutive structure of cells that functions as a high affinity system of releasing Са2+ ions from the cytoplasm and ensures a long-term maintenance of the basal concentration of these cations in the state of dormancy. Currently, there are no satisfactory means for the pharmacological correction of plasma membrane calcium ATPase function. Thus, elaboration, synthesis, and study of substances with the targeted impact on plasma membrane calcium ATPase are topical issues. Previously, we determined the ability of this calix[4]arene in the concentration of 10 µM to inhibit the contractive activity and to slow down the relaxation of smooth muscle of the myometrium in the NO-dependent way, which considerably decreases the normalized maximal velocity of the relaxation phase. Materials and Methods. The tenzometric methods and mechanokinetic analysis were used to investigate the impact of the cumulative increase in the concentration of calix[4]arene С-90 (10 nM – 100 µM) on the spontaneous contractive activity of the myometrium of rats. The complete profile of spontaneous cycles of contractions-relaxations was studied by the empirical multiparameter method of complex mechanokinetic analysis, elaborated by us (with the consideration of the parameters of time (τ0, τC and τR), force (Fmax, FC and FR), velocity (VC and VR), and impulse (Іmax, ІC and ІR). Results. Calix[4]arene C-90 evoked the dose-dependent inhibition of spontaneous contractive activity of the myometrium preparations. Its high concentrations caused a change in the structure of the contraction act, such as an increase in the duration of the contraction phase, while the duration of the relaxation phase did not show any changes. The multiparameter method of the complex mechanokinetic analysis demonstrated that in the whole range of the investigated concentrations, substance С-90 considerably decreases the indices of force parameters (Fmax, FC and FR) and the values of impulses of force Іmax, IC and IR of the spontaneous contractions of the myometrium. On the background of all the applied concentrations (10-7–10-4 М), calix[4]arene С-90 conditioned the slowing down of the relaxation of spontaneous contractions in uterine muscle preparations of rats, which was reflected in a reliable decrease in the parameter for the maximal velocity of the relaxation phase (VR). Conclusions. The results of the study demonstrate that calix[4]arene С-90 inhibits the processes of Са2+ extrusion from smooth muscle cells myoplasm, probably, impacting plasma membrane calcium ATPase molecules directly. It is noteworthy that C-90 is also likely to inhibit the processes of the intake of these cations to cells from the extracellular medium, causing a decrease in the velocity of force intensification during the contraction phase, and reducing the frequency and force of the spontaneous contractions in the myometrium.

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