Contemporary research has been enriched by the new directions in which the light plays a key role as a tool for modulation of cellular activity and invasive monitoring of intracellular ions and other components. The main advantages of these approaches are the possibilities to precisely control the intensity, spectral characteristics and durations of light signals in space and time. This review summarizes the key areas, optogenetics and photopharmacology, - directions that allow to control cellular activity with light. Optogenetics is the use of light-sensitive transmembrane proteins capable of exciting or inhibiting cellular activity under illumination by different wavelengths. In 2003 a light-sensitive protein canalo-rodopsine was isolated and cloned which is capable of inducing ion currents and changing cellular rest potential with its excitation under the blue light when embedded into the neurons or other cell types. Inhibition of cellular activity is caused by expression of other lightsensitive proteins - chloride or hydrogen pumps, or anion-selective ion channels. These principles turns out to be efficacious for the study of the functions of solitary cells and neural nets as well as for the control of living organisms behavior but their use in medicine is complicated because of necessary genetic manipulations. Photopharmacology is based on creating and using of chemical compounds changing conformations and/or activity under the light. Photochromic compounds with the use of photosensitive switches are capable of selective activation or inhibition of the activity of functionally important proteins - receptors, ion channels, enzymes, etc. The principles and the potential use of optogenetics and photopharmacology in the analysis of the neuronal functions and the perspectives for new approaches to treat some diseases of the nervous system are discussed.
Ricardo Miledi (16.09.1927-18.12.2017) is an outstanding neurophysiologist and biophysicist who made a great contribution to the study of synaptic transmission functions. He proved the key role of сalcium ions in the release of neuromediators, developed methods of receptor expression and membrane fragments integration into large oocytes that provided huge possibilities for thousands of researchers to study subtle mechanisms of transmembrane proteins function in norm and pathology. Ricardo Miledi received his MD degree in the National Autonomous University of Mexico and in 1954 he defensed his dissertation on the study of electrical nature of cardiac fibrillation in the National Institute of Cardiology (Mexico). In 1956-1958 he underwent training in Canberra Health Research Institute (Australia) in the laboratory headed by John Eccles (Nobel Prize 1963). In 1958 R. Miledi was invited to the Department of biophysics of University College London where in cooperation with Bernard Katz (Nobel Prize 1970) made a number of important discoveries in the analysis of acetylcholine receptor expression in denervated mucle; determination of the role of calcium in neuromediators release; analysis of membrane noise on neuromediator application to neuromuscular synapses; study of the effect of antibodies from patients with myasthenia gravis on neuromuscular transmission. In the early 1980s Ricardo Miledi implemented the method of functional expression in Xenopus frog oocytes of receptors and ion channels from messenger ribonucleic acid (mRNA). His heritage running the gamut is presented in more than 500 articles.
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