High-affinity ouabain receptors: primary membrane sensors for ionizing radiation

Abstract

Although the high sensitivity of the Na/K pump in cell membrane to ionizing radiation is well known in literature, the individual role of different isoforms of pump in determination of its radio-sensitivity is not clear yet. This is the subject of the present investigation. Using isotope, electro-physiological and enzymological methods, the effect of γ-ionizing radiation on cell membrane voltage-current characteristics, acetylcholine-induced membrane current, ²²Na⁺ and ⁴⁵Ca²⁺ exchange between cells and bathing solution, Na+K⁺-ATPase activity, dose-dependent ouabain binding with cell membrane, intracellular cAMP and membrane phosphorylation in snail neurons were studied. The changes in neurons as a result of 30-min γ-radiation exposure of snails to 5.16 Ci/kg at the end of the first 30 min of post-radiation period were as follows: the increase in membrane ionic conductance reversed the ouabain sensitivity of acetylcholine-induced currents, stimulation of ²²Na⁺ and ⁴⁵Ca²⁺ uptakes, inhibition of Na/K pump, activation Na/Ca exchange in reversed mode, increase in ouabain binding with high-affinity α₃ and decrease with α₂ middle-affinity receptors, decrease in intracellular cAMP content and membrane dephosphorylation. On the basis of the obtained data, it is suggested that both α₃ and α₂ catalytic subunits of Na⁺+K⁺-ATPase serve primary membrane sensors through the activation of which the biological effect of γ-radiation on neurons is realized. The IR has activation effects on α₃-dependent Na⁺/Ca²⁺ exchange in forward and its inactivation on α₂-dependent reverse modes.