Mg(2+),ATP-dependent plasma membrane calcium pump of smooth muscle cells. ІІ. Regulation of activity

Modulating the mechanokinetics of spontaneous contractions of the myometrium of rats using calix[4]arene C-90 – plasma membrane calcium ATPase inhibitor

“…As the previous biochemical studies had decisively proven that calix [4]arene С-90 has selective influence on the systems of primary active transport of Са 2+ into uterine SMC (first and foremost, due to PMCA inhibition) [4,22,23], our further studies were related to the mechanokinetic analysis of relaxation processes of spontaneous phase contractions of the myometrium preparations. The relaxation process in visceral SM is accompanied by a reduction in the intracellular concentration of Са 2+ ions in the myoplasm [7,10,17,[19][20][21].…”

“…Besides, due to an increased repolarization of PM, activation of Ca 2+ -sensitive K + -channels and increased work of Na + ,K + -ATPase lead to relaxation [24,25]. Experiments on the model of the PM suspension of pig uterine myocytes have shown that in addition to a significant inhibition of PMKA, calixarene C-90 is capable of suppressing the CPKA (I 50 values for PMKA and CPKA are 20.2±0.5 μM and 57.0±1.4 μM, respectively) to some extent [22]. As shown by A. Shmigol et al [15] blocking CPKA with thapsigargin causes prolongation of Ca 2+ -transientives caused by agonists, and plays a significant role in the generation of spontaneous contractions in uterus.…”

“…Recent studies have found that some substances that belong to the class of calixarenes are capable of selective inhibition of Са 2+ , Mg 2+ -ATPase of PM; for instance, calix [4]arene С-90 impacts this system with І 0.5 = 34.6±6.4 µM [4,9,22,23]. Previously, we determined the ability of this calix [4]arene in the concentration of 10 µM to inhibit the contractive activity and to slow down the relaxation of SM in the myometrium in the NO-dependent way, which considerably decreases the normalized maximal velocity of the relaxation phase [3].…”

Calix[4]arene С-956 selectively inhibits plasma membrane Са(2+),M(2+)-АТРase in myometrial cells

“…Since the main source of Ca 2+ for myometrium contraction is the extracellular space, the PM Ca 2+ ,Mg 2+ -ATPase is a leading "player" in the Ca 2+ release from the myometrial SM cells after contraction [10]. In addition, this enzyme maintains a strict control of the [Ca 2+ ] i level in the myometrial cells in a rest state by compensating the passive Ca 2+ entry via PM [11]. During one catalytic cycle, the Mg 2+dependent Ca 2+ pump transports one Ca ion against the concentration gradient using the energy of the hydrolysis of one ATP molecule [11,12].…”

“…In addition, this enzyme maintains a strict control of the [Ca 2+ ] i level in the myometrial cells in a rest state by compensating the passive Ca 2+ entry via PM [11]. During one catalytic cycle, the Mg 2+dependent Ca 2+ pump transports one Ca ion against the concentration gradient using the energy of the hydrolysis of one ATP molecule [11,12]. The catalytic function of PM Ca 2+ ,Mg 2+ -ATPase, as a fine regulator of the cytosolic Ca 2+ concentration, is described with such enzyme properties -high affinity to Ca 2+ , but the reaction catalyzed by this enzyme has much smaller turnover number compare to Na + / Ca 2+ exchanger [7,11].…”