Department: Department of Pharmacology and Toxicology

Email: viktor.yarotskyy@vcuhealth.org

Address/Location:
Hermes A. Kontos Medical Sciences Bldg, Room 411
1217 E Marshall St
Richmond, VA 23298

Education:

Ph.D. Biophysics (2002) Ukraine - Bogomoletz Institute of Physiology
MS Radiophysics (1998) Ukraine - Taras Shevchenko National University, Kyiv 
BS Radiophysics (1996) Ukraine - Taras Shevchenko National University, Kyiv

Research interests

 

Ion channels and transporters are transmembrane proteins that are essential for life by mediating critical functions such as neuronal excitability and plasticity (including voluntary and in voluntary neurobehavior), as well as muscle contraction, hormone secretion, cell-to-cell communication, and intracellular signaling. There are over one hundred unique ion channel types known, and the list keeps growing.

Our goal is to understand the pathophysiology of ion channels and how the dysfunction might be treated pharmacologically. Currently, we are attempting to understand the mechanisms by which opioids and HIV-1 interact synergistically to alter neuronal excitability and trigger neurodegeneration by dysregulating neuronal plasma membrane ion channel functions and intracellular ion homeostasis. Specifically, this includes neuronal voltage-gated calcium, potassium, sodium, and chloride channels, and ionotropic glutamate and GABA receptors that are disrupted by opioid and HIV-1 co-exposure.

In collaboration with Drs. Kurt F. Hauser (in Pharmacology and Toxicology) and Pamela E. Knapp (in Anatomy and Neurobiology), we have been developing a mechanistic model of how opioids and HIV-1 proteins exacerbate excitotoxicity by dysregulating chloride homeostasis and GABAergic disinhibition of neuronal excitation. We propose that the altered chloride homeostasis in neurons is a result of the dysregulation of several chloride transporters and voltage-gated chloride channels that until recently have been largely ignored.  We predict that understanding the role(s) of chloride channels and transporters in neuroHIV will ultimately translate into novel pharmacotherapies to treat opioid use disorder and neuroHIV, and potentially other neurological and neuropsychiatric disorders. We employ electrophysiological, genetic, imaging, behavioral, and molecular biological techniques and strategies to answer key questions in our research.

Selected publications:

1. Yarotskyy, V., Lark, A.R.S., Nass, S.R., Hahn, Y.K., Marone, M.G., McQuiston, A.R., Knapp, P.E., Hauser, K.F.(2022) Chloride channels with ClC-1-like properties differentially regulate the excitability of dopamine receptor D1- and D2-expressing striatal medium spiny neurons, American Journal of Physiology - Cell Physiology 322, C395-C409.
2. Lark, A.R.S., Silva, L.K., Nass, S.R., Marone, M.G., Ohene-Nyako, M., Ihrig, T.M., Marks, W.D., Yarotskyy, V., McQuiston, A.R., Knapp, P.E., Hauser, K.F. (2022) Progressive Degeneration and Adaptive Excitability in Dopamine D1 and D2 Receptor-Expressing Striatal Neurons Exposed to HIV-1 Tat and Morphine. Cellular and Molecular Neurobiology. Epub 2022/06/14. doi: 10.1007/s10571-022-01232-5.
3. Marks, W.D., Paris, J.J., Barbour, A.J., Moon, J., Carpenter, V.J., McLane, V.D., Lark, A.R.S., Nass, S.R., Zhang, J., Yarotskyy, V., McQuiston, A.R., Knapp, P.E., Hauser, K.F. (2021) HIV-1 Tat and Morphine Differentially Disrupt Pyramidal Cell Structure and Function and Spatial Learning in Hippocampal Area CA1: Continuous versus Interrupted Morphine Exposure, eNeuro, 8(3).
4. Yarotskyy V., Malysz J., Petkov G.V. (2019) Extracellular pH and intracellular phosphatidylinositol 4,5-bisphosphate control Cl- currents in guinea pig detrusor smooth muscle cells. American Journal of Physiology - Cell Physiology 317, C1268-C1277.
5. Yarotskyy V., Malysz J., Petkov G.V. (2019) Properties of single channel and whole-cell Cl- currents in guinea pig detrusor smooth muscle cells. American Journal of Physiology - Cell Physiology, 316(5), C698-C710.
6. Linsley, J.W., Hsu, I-U, Groom L., Yarotskyy, V., Lavorato, M., Horstick, E.J., Linsley, D., Wang, W., Franzini-Armstrong, C., Dirksen, R.T., and Kuwada, J.Y. (2017) Congenital myopathy results from misregulation of a muscle Ca2+ channel by mutant Stac3. The Proceedings of the National Academy of Sciences (PNAS), 114(2), E228-E236.
7. Yarotskyy, V., and Dirksen, R. T. (2014) RGK proteins: fashioning muscle with “Rad” new brakes. Channels (Austin) 8, 286-287
8. Yarotskyy, V., and Dirksen, R. T. (2014) Monovalent Cationic Channel Activity in the Inner Membrane of Nuclei from Skeletal Muscle Fibers. Biophysical journal 107, 2027-2036
9. Yarotskyy, V., Protasi, F., and Dirksen, R. T. (2013) Accelerated activation of SOCE current in myotubes from two mouse models of anesthetic- and heat-induced sudden death. PloS one 8, e77633
10. Yarotskyy, V., and Elmslie, K. S. (2012) Roscovitine inhibits CaV3.1 (T-type) channels by preferentially affecting closed-state inactivation. The Journal of pharmacology and experimental therapeutics 340, 463-472
11. Lanner, J. T., Georgiou, D. K., Dagnino-Acosta, A., Ainbinder, A., Cheng, Q., Joshi, A. D., Chen, Z., Yarotskyy, V., Oakes, J. M., Lee, C. S., Monroe, T. O., Santillan, A., Dong, K., Goodyear, L., Ismailov, II, Rodney, G. G., Dirksen, R. T., and Hamilton, S. L. (2012) AICAR prevents heat-induced sudden death in RyR1 mutant mice independent of AMPK activation. Nature medicine 18, 244-251
12. Yarotskyy, V., and Elmslie, K. S. (2010) Interference between two modulators of N-type (CaV2.2) calcium channel gating demonstrates that omega-conotoxin GVIA disrupts open state gating. Biochimica et biophysica acta 1798, 1821-1828
13. Yarotskyy, V., Gao, G., Du, L., Ganapathi, S. B., Peterson, B. Z., and Elmslie, K. S. (2010) Roscovitine binds to novel L-channel (CaV1.2) sites that separately affect activation and inactivation. The Journal of biological chemistry 285, 43-53
14. Yarotskyy, V., Gao, G., Peterson, B. Z., and Elmslie, K. S. (2009) The Timothy syndrome mutation of cardiac CaV1.2 (L-type) channels: multiple altered gating mechanisms and pharmacological restoration of inactivation. The Journal of physiology 587, 551-565
15. Yarotskyy, V., and Elmslie, K. S. (2009) Open-state occupancy prevents gating charge relaxation of N-type (CaV2.2) calcium channels. Biophysical journal 97, 2446-2455
16. Yarotskyy, V., and Elmslie, K. S. (2007) Roscovitine, a cyclin-dependent kinase inhibitor, affects several gating mechanisms to inhibit cardiac L-type (Ca(V)1.2) calcium channels. British journal of pharmacology 152, 386-395
17. Marchenko, S. M., Yarotskyy, V. V., Kovalenko, T. N., Kostyuk, P. G., and Thomas, R. C. (2005) Spontaneously active and InsP3-activated ion channels in cell nuclei from rat cerebellar Purkinje and granule neurones. The Journal of physiology 565, 897-910
18. Yarotskyy, V., Glushakov, A. V., Sumners, C., Gravenstein, N., Dennis, D. M., Seubert, C. N., and Martynyuk, A. E. (2005) Differential modulation of glutamatergic transmission by 3,5-dibromo-L-phenylalanine. Molecular pharmacology 67, 1648-1654

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