Cаlіx[4]аrene С-956 is effective inhibitor of Н(+)-Сa(2+)-exchanger in smooth muscle mitochondria

• Published in: Ukrainian biochemical journal Vol. 90; no. 1; pp. 25 - 33
• Main Authors: Danylovych, G. V., Kоlomiets, О. V., Danylovych, Yu. V., Rodik, R. V., Kаlchenko, V. I., Kоsterin, S. О.
• Format: Journal Article
• Language: English
• Published: National Academy of Sciences of Ukraine, Palladin Institute of Biochemistry 25.02.2018
• Subjects: calixarenes; H(+)-Ca(2+)-exchanger; mitochondria; smooth muscle; uterus
• ISSN: 2409-4943; 2413-5003
• DOI: 10.15407/ubj90.01.025

It was shown that calix[4]arene C-956 exhibited a pronounced concentration-dependent (10-100 μM) inhibitory effect on the H+-Ca2+-exchanger of the inner mitochondrial membrane of rat uterine myocytes (Ki 35.1 ± 7.9 μM). The inhibitory effect of calix[4]arene C-956 was accompanied by a decrease in the initial rate (V0) and an increase in the magnitude of the characteristic time (τ1/2) of the ΔрН-induced Са2+ release. At the same time, it did not affect the potential-dependent accumulation of Ca2+ in mitochondria. Thus, the action of calix[4]arene C-956 might be directed on increasing the concentration of Ca ions in the mitochondrial matrix. The calculation of basic kinetic parameters of the Ca2+ transport from isolated organelles (in the case of its non-zero stationary level), based on changes in fluorescence of Ca2+-sensitive dye Fluo-4 AM in mitochondria was performed. The proposed approach can be used for the kinetic analysis of the exponential decrease of the fluorescence response of any probes under the same experimental conditions.