Skip to main content
Log in

Photopharmacology: A Brief Review Using the Control of Potassium Channels as an Example

  • Published:
Neuroscience and Behavioral Physiology Aims and scope Submit manuscript

Photopharmacology is an area based on the creation of chemical compounds able to control the functioning of biological molecules using light. Photochromic compounds which activate or inhibit the activity of key cellular proteins, particularly ion channels, depending on the wavelength of the light, are powerful tools for noninvasive control of neural networks and, thus, for controlling the organs and behavior of animals. Photochromic substances can be divided into two main classes: (a) soluble photochromic ligands and (b) compounds covalently binding to target proteins, or tethered photochromic ligands. Potassium channel blockers, modulators of glutamate and GABA receptors, and cationic TRP channels have been created on this basis. Photopharmacology opens up the potential for controlling pain, restoring the photosensitivity of the retina, and controlling other physiological functions. This minireview will briefly present the main principles of the organization and actions of light-controlled switches, along with a description of photochromic chemical compounds able to modulate the activity of voltage-gated ion channels, and present preliminary investigations on the creation of photopharmacological compounds for therapeutic use.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Banghart, M. R., Mourot, A., Fortin, D. L., et al., “Photochromic blockers of voltage-gated potassium channels,” Angewandte Chemie Int. Ed. 48, 9097–9101 (2009).

    Article  CAS  Google Scholar 

  • Banghart, M., Borges, K., Isacoff, E., et al., “Light-activated ion channels for remote control of neuronal firing,” Nat. Neurosci., 7, 1381–1386 (2004).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Berg, J., Hung, Y. P., and Yellen, G., “A genetically encoded fluorescent reporter of ATP: ADP ratio,” Nat. Methods, 6, 161–6 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bilan, D. S., Pase, L., Joosen, L., et al., “HyPer-3: a genetically encoded H2O2 probe with improved performance for ratiometric and fluorescence lifetime imaging,” ACS Chem. Biol., 8, 535–42 (2013).

    Article  PubMed  CAS  Google Scholar 

  • Bregestovski, P. and Mukhtarov, M., “Optogenetics: perspectives in biomedical research (review),” Sovrem. Tekhnol. Med., 8, No. 4, 212–21 (2016).

    Article  Google Scholar 

  • Bregestovski, P. D., “Optogenetics in neurology: review of directions and perspectives,” in: Neurology in the 21st Century: Diagnostc, Therapeutic, and Research Techniques, Vol 3, Current Research Techniques in Experimental Neurology, M. A. Piradov et al. (eds.), ATMO, Moscow (2015), pp. 315–349.

  • Bregestovski, P., “Architecture of receptor-operated ion channels of biological membranes,” Biophysics, 56, No. 1, 51–64 (2011).

    Article  Google Scholar 

  • Bregestovski, P., Waseem, T., and Mukhtarov, M., “Genetically encoded optical sensors for monitoring of intracellular chloride and chloride-selective channel activity,” Front. Mol. Neurosci., 2, No. 15 (2009).

  • Buckingham, S. D., Kidd, J. F., Law, R. J., et al., “Structure and function of two-pore-domain K+ channels: contributions from genetic model organisms,” Trends. Pharmacol. Sci., 26, No. 7, 361–367 (2005).

    Article  PubMed  CAS  Google Scholar 

  • Busskamp, V., Duebel, J., Balya, D., et al., “Genetic reactivation of cone photoreceptors restores visual responses in retinitis pigmentosa,” Science, 329, 413–417 (2010).

    Article  PubMed  CAS  Google Scholar 

  • Chambers, J. J, Banghart, M. R., Trauner, D., and Kramer, R. H., “Light-induced depolarization of neurons using a modified Shaker K+ channel and a molecular photoswitch,” J. Neurophysiol., 96, No. 5, 2792–2796 (2006).

    Article  PubMed  CAS  Google Scholar 

  • Choi, K. L., Mossman, C., Aubé, J., and Yellen, G., “The internal quaternary ammonium receptor site of Shaker potassium channels,” Neuron, 10, No. 3, 533–541 (1993).

    Article  PubMed  CAS  Google Scholar 

  • Covington, H. E., Lobo, M. K., Maze, I., et al., “Antidepressant effect of optogenetic stimulation of the medial prefrontal cortex,” J. Neurosci., 30, 16082–16090 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Doyle, D. A., Morais Cabral, J., Pfuetzner, R. A., et al., “The structure of the potassium channel: molecular basis of K+ conduction and selectivity,” Science, 280, 69–77 (1998).

    Article  PubMed  CAS  Google Scholar 

  • Firsov, M. L., “Perspectives for the optogenetic prosthetization of the retina,” Zh. Vyssh. Nerv. Deyat., 67, No. 5 (2017).

  • Fortin, D. L., Banghart, M. R., Dunn, T. W., et al., “Photochemical control of endogenous ion channels and cellular excitability,” Nat. Meth., 5, No. 4, 331–338 (2008).

    Article  CAS  Google Scholar 

  • Fortin, D. L., Dunn, T. W., and Kramer, R. H., “Engineering light-regulated ion channels,” Cold Spring Harb. Protoc., 2011, No. 6, 579–585 (2011).

    Article  PubMed  Google Scholar 

  • Fritzsche, J., “Note sur les carbures d’hydrogène solides, tirés du gaudron de houille,” C.R. Acad. Sci., 69, 1035–1037 (1867).

    Google Scholar 

  • Gaub, B. M., Berry, M. H., Holt, A. E., et al., “Optogenetic vision restoration using rhodopsin for enhanced sensitivity,” Mol. Ther., 23, No. 10, 1562–1571 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Gorostiza, P., Arosio, D., and Bregestovski, P., “Molecular probes and switches for functional analysis of receptors, ion channels and synaptic networks,” Front. Mol. Neurosci., 6, 48 (2013).

  • Harvey, A. J. and Abell, A. D., “α-Ketoester-based photobiological switches: synthesis, peptide chain extension and assay against α-chymotrypsin,” Bioorg. Med. Chem. Lett., 11, No. 18, 2441–2444 (2001).

    Article  PubMed  CAS  Google Scholar 

  • Haubensak, W., Kunwar, P. S., Cai, H., et al., “Genetic dissection of an amygdala microcircuit that gates conditioned fear,” Nature, 468, 270–276 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Häusser, M., “Optogenetics: the age of light,” Nat. Methods, 11, 1012–1014 (2014).

    Article  PubMed  CAS  Google Scholar 

  • Hirshberg, Y., “Photochromie dans la serie de la bianthrone,” C.R. Acad. Sci., 231, No. 18, 903–904 (1950).

  • Imamura, H., Nhat, K. P. H., Togawa, H., et al., “Visualization of ATP levels inside single living cells with fluorescence resonance energy transfer-based genetically encoded indicators,” Proc. Natl. Acad. Sci. USA, 106, 15651–15656 (2009).

    Article  PubMed  Google Scholar 

  • Janovjak, H., Szobota, S., Wyart, C., et al., “A light-gated, potassium-selective glutamate receptor for the optical inhibition of neuronal firing,” Nat. Neurosci., 13, No. 8, 1027–1032 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kokel, D., Cheung, C. Y. J., Mills, R., et al., “Photochemical activation of TRPA1 channels in neurons and animals,” Nat. Chem. Biol., 9, No. 4, 257–63 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kramer, R. H., Mourot, A., and Adesnik, H., “Optogenetic pharmacology for control of native neuronal signaling proteins,” Nat. Neurosci., 16, 816–23 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  • Kuang, Q., Purhonen, P., and Hebert, H., “Structure of potassium channels,” Cell. Mol. Life Sci., 72, No. 19, 3677–3693 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Laprell, L., Hüll, K., Stawski, P., et al., “Restoring light sensitivity in blind retinae using a photochromic AMPA receptor agonist,” ACS Chem. Neurosci., 7, 15–20 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lima, S. Q. and Miesenböck, G., “Remote control of behavior through genetically targeted photostimulation of neurons,” Cell, 121, No. 1, 141–152 (2005).

    Article  PubMed  CAS  Google Scholar 

  • Macé, E., Caplette, R., Marre, O., et al., “Targeting channelrhodopsin-2 to ON-bipolar cells with vitreally administered AAV restores ON and OFF visual responses in blind mice,” Mol. Ther., 23, 7–16 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • MacKinnon, R. and Yellen, G., “Mutations affecting TEA blockade and ion permeation in voltage-activated K+ channels,” Science, 250, No. 4978, 276–279 (1990).

    Article  PubMed  CAS  Google Scholar 

  • MacKinnon, R., “Potassium channels,” FEBS Lett., 555, No. 1, 62–65 (2003).

    Article  PubMed  CAS  Google Scholar 

  • Miesenböck, G., “Optogenetic control of cells and circuits,” Annu. Rev. Cell Dev. Biol., 27, 731–58 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mourot, A., Kienzler, M. A., Banghart, M. R., et al., “Tuning photochromic ion channel blockers,” ACS Chem. Neurosci., 2, No. 9, 536–43 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Polosukhina, A., Litt, J., Tochitsky, I., et al., “Photochemical restoration of visual responses in blind mice,” Neuron, 75, No. 2, 271–82 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Rossi, M. A., Calakos, N., and Yin, H. H., “Spotlight on movement disorders: what optogenetics has to offer,” Mov. Disord., 30, 624–631 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  • Sahel, J. A. and Roska, B., “Gene therapy for blindness,” Annu. Rev. Neurosci., 36, 467–488 (2013).

    Article  PubMed  CAS  Google Scholar 

  • Sandoz, G. E. and Levitz, J., “Optogenetic techniques for the study of native potassium channels,” Front. Mol. Neurosci., 6, 6 (2013).

  • Sandoz, G., Levitz, J., Kramer, R. H., and Isacoff, E. Y., “Optical control of endogenous proteins with a photoswitchable conditional subunit reveals a role for TREK1 in GABA B signaling,” Neuron, 74, No. 6, 1005–1014 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Stawski, P., Sumser, M., and Trauner, D., “A photochromic agonist of AMPA receptors,” Angewandte Chemie International Edition, 51, 5748–5751 (2012).

    Article  PubMed  CAS  Google Scholar 

  • Szobota, S., Gorostiza, P., Del Bene, F., et al., “Remote control of neuronal activity with a light-gated glutamate receptor,” Neuron, 54, No. 4, 535–545 (2007).

    Article  PubMed  CAS  Google Scholar 

  • Tochitsky, I., Polosukhina, A., Degtyar, V. E., et al., “Restoring visual function to blind mice with a photoswitch that exploits electrophysiological remodeling of retinal ganglion cells,” Neuron, 81, No. 4, 800–813 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Tye, K. M. and Deisseroth, K., “Optogenetic investigation of neural circuits underlying brain disease in animal models,” Nat. Rev. Neurosci., 13, 251–66 (2012).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Velema, W. A., Szymanski, W., and Feringa, B. L., “Photopharmacology: beyond proof of principle,” J. Am. Chem. Soc., 136, 2178–2191 (2014).

    Article  PubMed  CAS  Google Scholar 

  • Wagner, F. B., Truccolo, W., Wang, J., and Nurmikko, A. V., “Spatiotemporal dynamics of optogenetically induced and spontaneous seizure transitions in primary generalized epilepsy,” J. Neurophysiol., 113, No. 7, 2321–2341 (2015).

    Article  PubMed  Google Scholar 

  • Wang, F., Bélanger, E., Paque, M. E., et al., “Probing pain pathways with light,” Neuroscience, 338, 248–271 (2016).

    Article  PubMed  CAS  Google Scholar 

  • Williams, J. C. and Denison, T., “From optogenetic technologies to neuromodulation therapies,” Sci. Transl. Med., 5, No. 177 (2013).

  • Yamamoto, K., Tanei, Z. I., Hashimoto, T., et al., “Chronic optogenetic activation augments Aβ pathology in a mouse model of Alzheimer disease,” Cell Rep., 11, No. 6, 859–865 (2015).

    Article  PubMed  CAS  Google Scholar 

  • Yue, L., Pawlowski, M., Dellal, S. S., et al., “Robust photoregulation of GABA(A) receptors by allosteric modulation with a propofol analogue,” Nat. Commun., 3, 1095 (2012).

  • Zhou, M., Morais-Cabral, J. H., Mann, S., and MacKinnon, R., “Potassium channel receptor site for the inactivation gate and quaternary amine inhibitors,” Nature, 411, No. 6838, 657–661 (2001).

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to P. D. Bregestovski.

Additional information

Translated from Zhurnal Vysshei Nervnoi Deyatel’nosti imeni I. P. Pavlova, Vol. 67, No. 5, pp. 41–52, September–October, 2017.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bregestovski, P.D., Maleeva, G.V. Photopharmacology: A Brief Review Using the Control of Potassium Channels as an Example. Neurosci Behav Physi 49, 184–191 (2019). https://doi.org/10.1007/s11055-019-00713-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11055-019-00713-3

Keywords

Navigation