KINETICS OF RELAXATION OF RAT MYOMETRIUM IN CONDITIONS OF INHIBITION OF PLASMA MEMBRANE CALCIUM PUMP AND SYSTEMS OF ACTIVE Са2+ TRANSPORT OF INTRACELLULAR Са2+-DEPOT

Abstract

The processes of regulation of smooth muscle contractile function depend greatly on the efficiency of maintaining Са²⁺-homeostasis by systems of active ionic transport of the plasma membrane (calcium pump and Na⁺,Ca²⁺-exchanger) and intracellular stores (sarcoplasmic reticulum and mitochondria). In this work, the effect of calixarene C-716 (macrocyclic compound capable of blocking functioning of the plasma membrane calcium pump) on the kinetics of relaxing K⁺-induced contraction of rat myomet­rium smooth muscles, while inhibiting the systems of active transport of calcium ions of intracellular Са²⁺-stores, were investigated. It was established that the application of 100 mM calixarene at the maximum of the phase component of the K⁺-induced contractile response did not change the kinetic parameters of the relaxation process (the normalized maximal velocity of relaxation phase V_nr and the half-maximal time of relaxation τ_1/2). The tonic component of K⁺-induced contraction remained without statistically significant changes. Blocking of Са²⁺-accumulating function of mitochondria by the protonophore СССР caused a significant increase in both the parameter V_nr and the tonic component of K⁺-induced contraction, while the τ_1/2 index remained at the control level. Blocking calcium pump of sarcoplasmatic reticulum with thapsigargin (TG) caused a conside­rable increase in the τ_1/2 ,V_nr parameters and the tonic component of the K⁺-induced contraction. Combination of TG and СССР induce further increase in the V_nr parameter and the tonic component of K⁺-induced contraction. The action of calixarene С-716 (100 mM) at the background of the impact of TG and СССР was accompanied by further increase in the tonic contraction, V_nr remained at the increased level, and the τ_1/2 index decreased. Possible mechanisms for changing the mechanokinetic parameters of relaxing K⁺-induced contraction of myometrium is discussed. Analysis of the results of our experimental data and the data of other researchers allow predicting that an increase in the rate of relaxation of myometrium smooth muscles at the action of calixarene C-716 under the conditions of blockage of intracellular Ca²⁺ depots is associated with a significant activation of NO synthesis by constitutive forms of NO-synthases, whereas an increase in the tonic component of K⁺-contraction under these conditions is probably due to an elevated concentration of Ca²⁺ ions in the myocytes.