Involvement of KАТР-channels of plasma and mitochondrial membranes in maintaining the contractive function of myometrium of non-pregnant rat uterus

Tsymbalyuk, O. V.; Vadzyuk, O. B.

doi:10.30970/sbi.1402.622

Cited by 3 publications

(2 citation statements)

References 32 publications

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“…Since the formulas used for calculation of the velocity parameters do not take into account the impacts of the change in force components, we calculated amplitude-independent normalized maximum velocities of the contraction and relaxation phases (Vn C and Vn R ) (Burdyga & Kosterin, 1991;Tsymbalyuk & Vadzyuk, 2020). As in the case of V C and V R , the normalized Vn C and Vn R indicators significantly decreased: the Vn C parameter was on average 29.6% and Vn R -on average 17.1% relative to the corresponding control parameters (in both cases n = 7, p <0.001).…”

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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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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“…A considerable (by one-third) acceleration of the relaxation process is especially noteworthy. This controversial effect (regarding the effect of only C-1087 on V R ) may be caused by Са 2+ -regulated processes, including a probable increase in the outflow of K + ions via Са 2+ -sensitive K + -channels (K Са ) of PM which are essential regulators of myometrium relaxation (Brainard et al, 2007;Tsymbalyuk & Vadzyuk, 2020). Also, under the conditions of higher [Ca 2+ ] i level, especially in the near-membrane areas, there should be a considerable increase in the activity of NO-synthases during PMCA blockage (Floyd & Wray, 2007;Pehlivanoğlu et al, 2013;Krebs, 2023); previously, we showed that the increase in NO concentration accelerated the process of myometrium relaxation (Kosterin et al, 2016).…”

Section: Serca Activity Blockingmentioning

confidence: 99%

Thapsigargin-resistant thiacalix[4]arene C-1087-sensitive component of the contractile activity in rat myometrium reflects the functioning of plasma membrane calcium pump

Tsymbalyuk,

Veklich,

Rodik

et al. 2023

Biol. Stud.

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Background. According to existing knowledge, thiacalix[4]arene С-1087 is highly capable of inhibiting Са2+-pump (Са2+, Mg2+-АТРase) of the plasma membrane; at the same time it inhibits the functioning of Са2+-pump of the sarcoplasmic reticulum of uterine smooth muscles to some degree. The aim of this research was to study the effects of С-1087 on the concentration of Ca2+ ions and contractile activity of the rat myometrium cells using an inhibitor of Са2+-pump of the sarcoplasmic reticulum – thapsigargin. Materials and Methods. The experiments were conducted using outbred white non-pregnant rats. The contractile activity in the preparations of longitudinal SM of uterine horns with preserved endothelium was registered in the isometric mode. To determine the changes in [Ca2+]i level, myocytes were treated with probes Hoechst 33342 (to test the nucleus of the cell) and fluo-4 AM (to test the change in Са2+-concentration in the cell). Results. The tenzometric studies with the subsequent mechanokinetic analysis demonstrated that under the action of thapsigargin (0.5 µM), thiacalix[4]arene C-1087 (10 µM) caused considerable changes in the kinetics of the spontaneous contractile activity processes in the myometrium of rats, including the decrease in the maximal contraction velocity and the increase in the maximal relaxation velocity. By means of confocal microscopy with Ca2+-sensitive fluorescent probe fluo-4, it was demonstrated that the application of thiacalix[4]arene С-1087 to immobilized myocytes of the uterus against the background of thapsigargin caused a transient spike of Са2+-signal with the subsequent turn of the intracellular concentration of Ca ions to the stable increased level. The effects of С-1087 under the action of thapsigargin regarding the relaxation phase in the spontaneous myometrium contractions were removed after the preliminary blocking of nitric oxide synthases L-NAME (100 µM). Under the action of L-NAME, thiacalix[4]arene С-1087 (10 µM) caused complete inhibition of the relaxation process in the contraction of myometrium preparations, induced by high-potassium solution (80 mM). Conclusions. The primary reason for changes in the contractile activity and Ca2+-signal in uterine myocytes under the effect of thiacalix[4]arene С-1087 is its ability to inhibit Са2+-pump of the plasma membrane; further С-1087-induced changes in the smooth muscle tissues may be caused by the increased level of Са2+ concentration in myocytes. The obtained results demonstrate thiacalix[4]arene С-1087 is a promising compound for the elaboration of pharmacological preparations for modulating the contractile activity in smooth muscles, including myometrium.

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Participation of KАТР-channels of plasma and mitochondrial membranes in the regulation of mechanokinetics of rat myometrium spontaneous contractions

et al. 2022

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Background. ATP-sensitive K+ channels of the plasma membrane in the smooth muscles of the uterus are one of the most significant ion channels that regulate the excitability of this tissue both in the non-pregnant state and during pregnancy. MitoKATР-channels ensure regulation of the bioenergetic state of mitochondria (the intensity of mitochondrial respiration and the potential of the inner mitochondrial membrane). Thus far, there is no information on the participation of both types of these channels in the regulation of the mechanokinetics of spontaneous contractions, therefore the aim of this work was to perform a complete mechanokinetic analysis of spontaneous contractions of rat myometrium under conditions of blocking and activation of ATP-sensitive K+-channels of the plasma membrane and blocking of mitoKATP-channels. Materials and Methods. Experiments were performed on female Wistar rats. The spontaneous activity of smooth muscle stripes of longitudinal smooth muscles of uterine horns was registered by the tenzometric method in the isometric mode. The experiments used the activator of ATP-sensitive K+-channels of the plasma membrane diazoxide (50, 100, 150 and 200 μM) and the blocker of these channels glibenclamide (1, 2, 4, 6, 8 and 10 μM), as well as the blocker of ATP-sensitive mitochondrial K+-channels 5-hydroxydecanoate (5-HD, 50 µM). The study of 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 parameters (VC and VR). Results. It was found that both blocking and activation of plasma membrane KATP-channels cause suppression of the amplitude, probably according to different cellular mechanisms of regulation of ion conductivity. Under the influence of glibenclamide, a significant decrease in the frequency and mechanokinetic parameters of spontaneous contractions of the myometrium was observed, which confirms the contribution of plasma membrane KATP-channels to maintaining the excitability of the myometrium of non-pregnant rats. Activation of plasma membrane KATP-channels by diazoxide caused a change in individual mechanokinetic parameters of spontaneous contractions of the myometrium. Under the action of the mitoKATP-channel blocker 5-HD, suppression of the amplitude and modulation of the mechanokinetic parameters of the contraction phase was observed without changes in the kinetics of the relaxation phase of spontaneous contractions. Conclusions. Thus, modulation of the KATP-channels of the plasma membrane and mitochondria is accompanied by the suppression of spontaneous contractions of the myometrium. Both types of KATP-channels are important regulators of myometrial excitability, however, unlike plasma membrane KATP-channels, mitoKATP-channels probably do not modulate the processes of extrusion of Ca2+ from the cytosol.

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Involvement of KАТР-channels of plasma and mitochondrial membranes in maintaining the contractive function of myometrium of non-pregnant rat uterus

Cited by 3 publications

References 32 publications

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

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

Thapsigargin-resistant thiacalix[4]arene C-1087-sensitive component of the contractile activity in rat myometrium reflects the functioning of plasma membrane calcium pump

Participation of KАТР-channels of plasma and mitochondrial membranes in the regulation of mechanokinetics of rat myometrium spontaneous contractions

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