Tag Archives: smooth muscle cell

Inhibition of Na(+),K(+)-ATPase and activation of myosin ATPase by calix[4]arene C-107 cause stimulation of isolated smooth muscle contractile activity

T. O. Veklich1, R. D. Labyntseva1, O. A. Shkrabak1, O. V. Tsymbalyuk2,
R. V. Rodik3, V. I. Kalchenko3, S. O. Kosterin1

1Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
2Institute of High Technologies, Taras Shevchenko National University of Kyiv, Ukraine;
3Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: veklich@biochem.kiev.ua; otsymbal@bigmir.net; manli@ioch.kiev.ua

Received: 04 Jule 2019; Accepted: 29 November 2019

The discovery of compounds that might modify myometrial contractility is an important area of researches. In our previous experiments, we found that some representatives of macrocyclic compounds fami­ly – calix[4]arenes – can modify the enzymatic and transport activity of membrane-bound cation-transport ATP hydrolases. The aim of this work was to study and compare the effect of calix[4]arene C-107 on the enzymatic activities of Mg2+-dependent ATPases of the uterine smooth muscle, namely: ouabain-sensitive Na+,K+-ATPase, plasma membrane Ca2+-independent “basal” Mg2+-ATPase, ATPase of the actomyosin complex and myosin subfragment-1, with effect on the contractile activity of the myometrium. It was shown that calix[4]arene C-107 efficiently inhibited myometrium Na+,K+-ATPase (I50 = 54 ± 6 nM) selectively to other ATP-hydrolases of the plasma membrane and simultaneously activated the enzymatic activity of the myosin ATPase of smooth muscles (A50 = 9.6 ± 0.7 μM). Such reciprocal biochemical effects led to the stimulation of the smooth muscle contractile activity that was demonstrated by the tensometric method using different isolated smooth muscles. Calix[4]arene С-107 was shown to stimulate the increase of the tonic component of myometrium contractions induced by oxytocin, as well as contractions of the caecum muscles induced by high-potassium solution or acetylcholine, and to maintain increased tension for a long time. Thus, calix[4]arene C-107 is a prospective compound for enhancing the smooth muscle basal tone and/or contraction in case of hypotonic dysfunctions.

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

T. О. Veklich, Iu. Iu. Mazur, S. О. Kosterin

Palladin Institute of Biochemistry, National Academy of Science of Ukraine, Kyiv;
e-mail: veklich@biochem.kiev.ua,
yuliya.vorona@gmail.com

Plasma membrane Ca2+-pump is one of key proteins, which takes part in Ca2+ exchange in smooth muscle cells. It has a lot of diverse functions from control of basal cytoplasmal Ca2+ concentration to regulation of proteins  involved in Ca2+-dependent signal pathway. Ca2+ pump function is often depen­dent on the isoform or even form of alternative splicing. Allowing for a variety of Ca2+-pump functions and properties, which were reviewed in detail in the first part of our review article cycle (Ukr. Biochem. J., 2015; 87(1)), the precise control of the mentioned pump activity is very important for cell functioning­. The other part of this article is dedicated to different regulation factors of smooth muscle plasma membrane Ca2+-pump activity: endogenous and exo­genous, biotic and abiotic factors. Special attention is given to literature data and own results about design and the search of selective plasma membrane Ca2+-pump inhibitor which would allow examining its functioning in smooth muscle cells more meticulously.

Mg(2+),ATP-dependent plasma membrane calcium pump of smooth muscle cells. I. Structural organization and properties

T. O. Veklich, Iu. Iu. Mazur, S. O. Kosterin

Palladin Institue of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: veklich@biochem.kiev.ua; yuliya.vorona@gmail.com

Tight control of cytoplasm Ca2+ concentration is essential in cell functioning. Changing of Са2+ concentration is thorough in smooth muscle cells, because it determines relaxation/constraint process. One of key proteins which control Са2+ concentration in cytoplasm is Mg2+,ATP-dependent plasma membrane calcium pump. Thus, it is important to find compoumds which allowed one to change  Mg2+,ATP-dependent plasma membrane calcium pump activity, as long as this topic is of current interest in biochemical research which regards energy and pharmacomechanical coupling mechanism of muscle excitation and contraction. In this article we generalized literatute and own data about properties of smooth muscle cell plasma membrane Ca2+– pump. Stuctural oganization, kinetical properties and molecular biology are considered.