Calix[4]arene C-715 modulates mitochondrial functioning and contractile activity of uterine smooth muscle

Aim. To elucidate the effects of calix[4]arene C-715 on the contractile activity of myometrial strips and the Ca2+-dependent functional activity of mitochondria. Materials and Methods. Confocal imaging was performed on Wistar rats myocytes using MitoTracker Orange CM-H2TMRos and FITC-labeled compound C-1308. NADH autofluorescence, energy-dependent Ca2+ accumulation, and NO generation in the isolated mitochondria were measured by spectrofluorimetry and flow cytometry. The contractile activity of rat's myometrium was recorded in the isometric mode. The hydrodynamic diameter of myocytes was assessed by laser correlation spectroscopy. Results. C-1308 accumulates in myocytes and colocalizes with MitoTracker, confirming the ability of C-715 to interact with mitochondria. A mechano-kinetic analysis showed that C-715 at 30 μM enhances the amplitude, frequency, force, temporal, and impulse parameters of spontaneous contractions while reducing the velocity. C-715 at 30 μM inhibited NO synthesis in intact myocytes and mitochondria; at 10–30 μM suppressed NADH oxidation and energy-dependent Ca2+ accumulation, which correlate with the contractility increase and the decrease in the hydrodynamic diameter of myocytes. Conclusions. The action of C-715 is directed at reducing Ca2+ transport activity and Ca2+- dependent processes in mitochondria, resulting in an enhancement of myometrial contractility.