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
DOI: http://dx.doi.org/10.30970/sbi.1202.565
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 Vnr and the half-maximal time of relaxation τ1/2). 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 Vnr and the tonic component of K+-induced contraction, while the τ1/2 index remained at the control level. Blocking calcium pump of sarcoplasmatic reticulum with thapsigargin (TG) caused a considerable increase in the τ1/2 ,Vnr parameters and the tonic component of the K+-induced contraction. Combination of TG and СССР induce further increase in the Vnr 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, Vnr remained at the increased level, and the τ1/2 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.
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