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

Abstract

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.

Keywords

• myometrium
• katp-channels of the plasma membrane and mitochondria
• spontaneous contractions
• mechanokinetic analysis