INVOLVEMENT OF KАТР-CHANNELS OF PLASMA AND MITOCHONDRIAL MEMBRANES IN MAINTAINING THE CONTRACTIVE FUNCTION OF MYOMETRIUM OF NON-PREGNANT RAT UTERUS

Abstract

K⁺-channels, in particular, ATP-sensitive K⁺-channels of plasma and inner mitochondrial membranes, play a significant role in regulating the contraction-relaxation processes in visceral smooth muscles. The specificities of these channels and their role in maintaining excitation have been well investigated for the cardiac muscle and smooth vascular muscles. However, scarce data exist about the involvement of these channels, especially the mitochondrial ones, in regulating myometrium contractions. The tenzometric methods and mechanokinetic analysis were used to study the regularities in oxytocin-induced contractions of smooth muscles of non-pregnant rats myometrium under the conditions of modulating ATP-sensitive K⁺-channels of plasma and inner mitochondrial membranes. It was determined that prior incubation of myometrium in the presence of the blocking agents of K_ATP-channels of plasma membrane and mitochondria (glibenclamide and 5-hydroxydecanoate, respectively) was generally associated with the increase in the phase and, in some cases, tonic components of oxytocin-induced contractions. There was an increase in the amplitude of oxytocin-induced contractions at the background of the impact of glibenclamide (the range of concentrations used was 1–10 µM) without significant changes in the area under these mechanograms; the velo­city of relaxation increased considerably as well. The blocking agent of mitochondrial ATP-sensitive K⁺-channels, 5-hydroxydecanoate (in the concentrations of 50 µM and 200 µM) caused considerable changes in the kinetics of the processes of intensification (the increase in velocity) and decline (more than 2-fold decrease in the velocity) in comparison with the force of oxytocin-induced contractions, but it did not impact their amplitude and the area under mechanograms. The most significant effect, demonstrated by the activator of ATP-sensitive K⁺-channels of diazoxide (the range of concentrations was 50–200 µM), was the reduction in the area under oxytocin-induced contractions by half. This compound also caused a decrease in the amplitude of contractions and a considerable increase in the maximal velocities of the intensification and decline phases for the force of oxytocin-induced contractions. The combined effect of the blo­cking agents of K_ATP-channels of plasma and inner mitochondrial membranes, glibenclamide (10 µM) and 5-hydroxydecanoate (200 µM), was accompanied by the increase in the amplitude of oxytocin-induced contractions and the changes in the kinetics of contraction and relaxation processes. Thus, the data obtained demonstrate that K_ATP-channels of plasma membrane and mitoK_ATP-channels in non-pregnant rats’ myome­trium play a modulating role in forming the contractive response to the uterotonic hormone oxytocin. These channels are involved in the regulation of the contractive function of myometrium, modulating the amplitude of contractions, the ability of long-term strain support and the kinetics of contraction and relaxation processes.