S. O. Kosterin

Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine,
Department of Muscle Biochemistry, Kyiv;
e-mail: kinet@biochem.kiev.ua

Received: 12 May 2025; Revised: 18 June 2025;
Accepted: 30 October 2025; Available on-line: 02 December 2025

In this scientific-historical review devoted to the recent achievements of the Muscle Biochemistry Department of the Palladin Institute of Biochemistry, the NAS of Ukraine, we synthesize findings from interdisciplinary investigations of intracellular calcium homeostasis in smooth muscle (exemplified by the myometrium) conducted at the interface of biochemistry, physical and organic chemistry, biophysics, and mathematical/computational modeling. We emphasize that the selected calix[4]arenes considered here act selectively as inhibitors of the Mg²⁺,ATP-dependent calcium and sodium pumps – ion-transporting ATPases (electroenzymes Ca²⁺,Mg²⁺-ATPase and Na⁺,K⁺-ATPase) – of the plasma membrane of smooth-muscle cells, enabling controlled modulation of intracellular Ca²⁺ homeostasis and the contractile activity of the myometrium. The data obtained also indicate that the selected calix[4]arenes can be regarded as compounds suitable for efficient investigation of mitochondrial function in smooth-muscle cells, in particular the mechanisms of transmembrane Ca²⁺ exchange, the principles governing membrane-potential formation, and the contribution of these subcellular structures to the control of the mechanokinetics of the contraction–relaxation cycle. It is shown that some calix[4]arenes act as effectors of the ATPase activity of contractile proteins and protect this activity from the inhibitory influence of heavy-metal ions. Taken together, these results outline biochemical approaches to the fine regulation of calcium fluxes and smooth-muscle contractility and underscore the potential of calix[4]arenes as selective “molecular platforms” useful for addressing fundamental and applied (biomedical) problems in contemporary physico-chemical muscle biology.

Keywords: Ca2+ signaling, Ca2+‚Mg2+-ATPase, calix[4]arenes, mitochondria, myometrium, Na+‚K+-ATPase, plasma membrane, smooth muscle, spontaneous contractions