Журнал эволюционной биохимии и физиологии, 2020, T. 56, № 7, стр. 737-737

The aim of the present study was to investigate molecular mechanisms of modulating action of effectors of Ca²⁺-activated big-conductance potassium channel (BK(Ca)) against toxicity and cell death evoked by heavy metal ions, cadmium (Cd²⁺). Experiments were conducted on two cell types (AS-30D, PC12) and isolated liver mitochondria of rat. Previously we observed that cytotoxic effects of Cd²⁺ decreased in the presence of paxilline - BK(Ca) blocker and enhanced in the presence of NS1619 or NS004 – BK(Ca) openers. In this work we have shown that both BK(Ca) activators under test induce apoptosis of AS-30D cells which is sensitive to paxilline. In the simultaneous presence of Cd²⁺ and NS1619 or NS004 in the incubation medium the apoptosis of AS-30D cells increased and paxilline had no influence on it. As recently obtained by us, paxilline does not induce apoptosis per se as well as does not affect the Cd²⁺-induced apoptosis of AS-30D cells. At the same time, paxilline produced transient decrease of maximal, i.e. completely uncoupled, respiration of AS-30D cells, and enlarged the intracellular production of reactive oxygen species, ROS. Besides, paxilline partially inhibited Cd²⁺-induced necrosis both of AS-30D and PC12 cells. Moreover, paxilline temporally depressed maximal respiration rate of PC12 cells as well and decreased their ROS production in the presence of Cd²⁺ (Belyaeva, Sokolova, 2020). Using PC12 cells, in the present work we have shown that NS1619 and NS004 do not change significantly the Cd²⁺-induced ROS generation. Interestingly, maximal decrease of the Cd²⁺-enhanced ROS formation was observed when PC12 cells were incubated with paxilline in the presence of NS1619 or NS004. The both BK(Ca) openers enhanced harmful effects of Cd²⁺ on respiration and membrane permeability of isolated rat liver mitochondria in incubation media of different ion content.

Supported by state assignment (АААА-А18-118012290371-3).