ISSN 1819-7124, Neurochemical Journal, 2009, Vol. 3, No. 2, pp. 87–92. © Pleiades Publishing, Ltd., 2009. Original Russian Text © T.N. Pitlik, P.M. Bulai, A.A. Denisov, D.S. Afanasenkov, S.N. Cherenkevich, 2009, published in Neirokhimiya, 2009, Vol. 26, No. 2, pp. 104–110. 87 INTRODUCTION Studies of mechanisms of redox-dependent regula- tion of cellular processes are one of the actively devel- oping directions of cell biology. Currently, reactive oxygen species (ROS) are considered not only as byproducts of aerobic metabolism but also as univer- sal secondary messengers in intracellular signaling. Under conditions of oxidative stress accompanied by an excess accumulation of ROS in the cells, redox reactions that involve ROS may result in a number of cell pathologies, including the development of neuro- degenerative diseases [1]. Currently, it is known that ROS may regulate the electric activities of neurons by changing the mem- brane potential and parameters of generation of action potentials. In addition, involvement of the ROS is nec- essary for induction of long-term potentiation, one of the forms of synaptic plasticity, which underlies such cognitive functions of the brain as memory and learn- ing [2]. However, the mechanisms of ROS action at the cellular level are unknown. The effects of extracellular oxidants on cell functions are mainly mediated by interactions with transport pro- teins and membrane phospholipids, which results in the modification of cell ionic homeostasis [3]. Neuronal ionic homeostasis is maintained by sev- eral ion transporting systems which include (1) ionic channels, such as calcium channels (voltage-depen- dent, and dihydropyridine-sensitive Ca 2+ channels of plasma membrane, intracellular ryanodine- and inosi- tol-1,4,5-triphosphate-sensitive Ca 2+ channels of endoplasmic reticulum), plasma membrane potassium channels (voltage-dependent K + channels, calcium- dependent K + channels, and ATP-dependent K + chan- nels), (2) ionic pumps such as the Ca 2+ -ATPases of the endoplasmic and sarcoplasmic reticulums, Na + /K + - ATPase, and proton ATPase, (3) ion exchangers, such as Na + /Ca 2+ -exchanger and the Cl – /HCO 3 -exchanger, and (4) ion cotransporters, such as the K + /Cl – -cotrans- porter, Na + /K + /Cl – -cotransporter, and Pi/Na + -cotrans- porter [3]. The major mechanisms of ROS action on these ion-transporting systems include (1) oxidation of sulf- hydryl groups of transport proteins, (2) lipid peroxida- tion, and (3) perturbation of oxidative phosphoryla- tion and decrease in intracellular ATP level [3]. The role of lipid peroxidation in the regulation of neuronal ionic homeostasis. Lipid peroxidation (LP) is a free radical oxidation of polyunsaturated fatty acids in biological systems. LP is one the main processes of damage of biological membranes, which develops in many pathological processes. LP is initiated by free radical attack of fatty acid by ROS, whose reactivity is high enough to detach a hydrogen atom from a methylene group. The presence of a double bond in a fatty acid weakens the C–H bond in the adjacent carbon atoms and, hence, facilitates detachment of a hydrogen atom. As a consequence, polyunsaturated fatty acids more frequently undergo lipid peroxidation [4]. The membranes of nerve cells are characterized by higher contents of unsaturated fatty acids, which increases the probability of initiation of LP in the presence of ROS. Formation of lipid peroxides, pri- mary products of LP, disturbs the functional state of the cell membrane due to changes in its fluidity and changes in the normal functioning of membrane pro- teins. This is accompanied by changes in the mem- brane permeability for different ions, such as calcium and hydrogen, and low-molecular substances. Redox Regulation of Ionic Homeostasis in Neurons T. N. Pitlik 1 , P. M. Bulai, A. A. Denisov, D. S. Afanasenkov, and S. N. Cherenkevich Belarus State University, Minsk, Belarus Received July 28, 2008 Abstract—We have summarized the data on the regulation of the functional activities of neurons by reactive oxygen species. We also discuss the mechanisms of regulation of neuronal ionic homeostasis by redox factors and the role of redox molecules in the intracellular transduction of signals. The sources of reactive oxygen spe- cies in neurons and their role in the synaptic plasticity and formation of long-term memory are considered. Key words: reactive oxygen species, ionic homeostasis, synaptic plasticity, intracellular signaling DOI: 10.1134/S1819712409020020 REVIEW ARTICLES 1 Corresponding author; address: prosp. Nezavisimosti 4, Minsk, 220030 Belarus; e-mail: tpitlik@mail.ru