Pharmacology

Yuriy M. Usachev, PhD

Portrait

Associate Professor of Pharmacology
Associate Professor of Anesthesia

Contact Information

Primary Office: 2-450 Bowen Science Building
Iowa City, IA 52242
Primary Office Phone: 319-335-9388

Lab: 2-440 Bowen Science Building
Iowa City, IA 52242
Phone: 319-353-3887

Email: yuriy-usachev@uiowa.edu

Education

BS, Physics - Optics and Spectroscopy, Kiev State University, Kiev, Ukraine
MSc, Physics—Optics and Spectroscopy, Kiev State University, Kiev, Ukraine
PhD, Biology, International Center of Molecular Physiology, Bogomoletz Institute of Physiology, Kiev, Ukraine

Visiting Scientist, Department of Neurophysiology, Max-Planck-Institute of Psychiatry, Munich, Germany
Postdoctoral Fellow, The Physiological Laboratory, University of Cambridge, Cambridge, United Kingdom
Research Scientist, International Center of Molecular Physiology, Bogomoletz Institute of Physiology, Kiev, Ukraine
Postdoctoral Fellow/Lecturer in Pharmacology, Department of Pharmacology, University of Minnesota, Minneapolis, Minnesota

Education/Training Program Affiliations

Biosciences Graduate Program
Interdisciplinary Graduate Program in Neuroscience
Medical Scientist Training Program

Research Summary

Chronic pain management remains one of the most serious public health problems. We use an array of molecular biological and genetic techniques, combined with patch-clamp recordings and fluorescent imaging of intracellular Ca2+, Na+ and pH changes in pain-conducting neurons (called nociceptors), as well as behavioral studies to address two broad sets of questions related to chronic pain pathogenesis. The first set of questions focuses on relatively rapid changes to nociceptor excitability and synaptic transmission that are induced by proinflammatory mediators generated by immune and glial cells at the site of injury or inflammation, and mediated via phosphorylation of so-called pain channels, including TRPV1, TRPA1 and voltage-gated Na+ channels Nav1.7, 1.8 and 1.9. We are particularly interested in the role of the complement system factors C3a and C5a in regulating nociceptor excitability and function. The second set of questions examines the long-term changes to the nociceptor molecular composition and function in response to injury or inflammation, and involves alterations in gene expression. We particularly focus on the Ca2+-dependent transcription factor NFAT that regulates expression of a number of proteins implicated in pain sensitization, such as COX-2, BDNF, chemokine receptor CCR2 and several voltage-gated K+ channels. Another line of investigation focuses on the function of mitochondria in regulating neuronal plasticity and survival under conditions of stress or illness, such as hyperglycemia in diabetes or exposure to toxic concentrations of glutamate following ischemic stroke. In addition to generating energy, mitochondria play critical role in neuronal signaling, and particularly, in the regulation of Ca2+ homeostasis and Ca2+-dependent processes. Impaired mitochondrial Ca2+ regulation contributes to neuronal damage in stroke and neurodegenerative disorders. Mitochondria are highly dynamic organelles that can rapidly undergo fission and fusion, and the mitochondrial fission and fusion (MFF) balance can significantly impact dendritic and axonal morphogenesis, synaptic plasticity and neuronal survival. We use a multidisciplinary approach (electrophysiology, confocal microscopy, brain slice recordings, animal models of diabetes and stroke) to better understand regulatory mechanisms and function of mitochondrial Ca2+ transport in neurons, its dependence on the MFF status, and the role of mitochondrial Ca2+ and MFF in protecting neurons from glutamate toxicity as well as hyperglycemia-induced axonal degeneration.

All Publications

Gong W, Kolker S, Usachev Y, Walder R, Boyle D, Firestein G, Sluka K.  Acid-Sensing Ion Channel 3 decreases phosphorylation of ERK and induces synoviocyte cell death by increasing intracellular calcium.  2014. 

Kim M, Shutov L, Ulrich J, Lin Z, Rysted J, Usachev Y.  NGF facilitates depolarization-induced activation of Ca2+ /calcineurin-dependent transcription NFAT in sensory neurons via the PI3K-Akt-GSK3 signaling pathway.  2014. 

Inagaki A, Frank A, Usachev Y, Benveniste M, Lee A.  Pharmacological correction of gating defects in the voltage- gated Cav2.1 Ca2+ channel due to a familial hemiplegic migraine mutation.  Neuron.  2014. 81:91-102.
[Link]

Shutov L, Warwick C, Gupte R, Shepherd A, Mohapatra D, Usachev Y.  The complement fragment C5a produces thermal hyperalgesia via TRPV1 and macrophage-dependent release of NGF.  2014. 

Shutov L, Warwick C, Gupte R, Shepherd A, Brennan T, Clark J, Mohapatra D, Usachev Y.  Complement C5a produces nociceptive sensitization via TRPV1 in mouse.  Abstract Viewer/Itinerary Planner. San Diego, CA: Society for Neuroscience (Poster).  2013. 

Shutov L, Kim M, Houlihan P, Medvedeva Y, Usachev Y.  Mitochondria and plasma membrane Ca2+ -ATPase (PMCA) control presynaptic clearance in capsaicin-sensitive rat sensory neurons.  Journal of Physiology.  2013. 591:2443-2462.
[Link]

Sowers L, Loo L, Wu Y, Campbell E, Ulrich J, Wu S, Paemka L, Wassink T, Meyer K, Bing X, El-Shanti H, Usachev Y, Ueno N, manak R, Shepherd A, Ferguson P, Richerson G, Mohapatra D, Wemmie J, Bassuk A.  PRICKLE2 defects link the non-canonical Wnt pathway to autism.  Molecular Psychiatry.  2013. 18:1077-1089.
[Link]

Ulrich J, Kim M, Houlihan P, Shutov L, Mohapatra D, Strack S, Usachev Y.  Distinct Activation Properties of the Nuclear Factor of Activated T-cells (NFAT) Isoforms NFATc3 and NFATc4 in Neurons..  J Biol Chem.  2012 November 2. 287(45):37594-37609.
[Link]

Loo L, Shepherd A, Mickle A, Lorca R, Shutov L, Usachev Y, Mohapatra D.  The C-Type Natriuretic Peptide Induces Thermal Hyperalgesia through a Noncanonical Gβγ-dependent Modulation of TRPV1 Channel.  J Neurosci.  2012 August 29. 32(35):11942-11955.
[Link]

Merrill R, Dagda R, Dickey A, Cribbs J, Green S, Usachev Y, Strack S.  Mechanism of neuroprotective mitochondrial remodeling by PKA/AKAP1.  PLoS Biol.  2011 April. 9(4):e1000612.
[Link]

Yorek M, Houlihan P, Slupe A, Usachev Y.  Mechanisms of TRPM8-mediated [Ca2+]i and electrical oscillations in sensory neurons.  IBRO 8th World Congress of Neuroscience (Poster), Florence, Italy.  2011. 

Shutov L, Kim M, Usachev Y.  Mitochondria and plasma membrane Ca2+-ATPase (PMCA) control presynaptic [Ca2+]i clearance in capsaicin-sensitive sensory neurons.  Abstract Viewer/Itinerary Planner. Washington DC: Society for Neuroscience (Poster).  2011. 

Houlihan P, Dickey A, Merrill R, Strack S, Usachev Y.  Mitochondria-targeted protein kinase A stabilizes Ca2+ homeostasis in hippocampal neurons exposed to toxic concentrations of glutamate.  Abstract Viewer/Itinerary Planner. Washington DC: Society for Neuroscience (Poster).  2011. 

Loo L, Shepherd A, Lorca R, Mickle A, Usachev Y, Mohapatra D.  Natriuretic peptides induce nociceptor sensitization by upregulating TRPV1 activity/expression.  Abstract Viewer/Itinerary Planner. Washington DC: Society for Neuroscience (Poster).  2011. 

Kolker S, Walder R, Usachev Y, Hillman J, Boyle D, Firestein G, Sluka K.  ASIC3 expressed in Type B synoviocytes and chondrocytes modulates hyaluronan expression and release.  Annals of the Rheumatic Diseases .  2010 May. 69(5):903-909.
[Link]

Jenkins M, Christel C, Jiao Y, Abiria S, Kim K, Usachev Y, Obermair G, Colbran R, Lee A.  Ca2+-dependent facilitation of Cav1.3 Ca2+ channels by densin and Ca2+/calmodulin-dependent protein kinase II.  J Neurosci.  2010 April 14. 30(15):5125-5135.
[Link]

Jang J, Clark J, Li X, Yorel M, Usachev Y, Brennan T.  Nociceptive sensitization by complement C5a and C3a in mouse.  Pain.  2010 February. 148(2):343-352.
[Link]

Ulrich J, Kim M, Usachev Y.  Distinct regulation of NFATc3 and NFAC4 in central and peripheral neurons.  Abstract Viewer/Itinerary Planner. San Diego, CA: Society for Neuroscience (Poster).  2010. 

Yorek M, R H, Slupe A, Usachev Y.  Mechanisms of TRPM8-mediated [Ca2+]i oscillations in sensory neurons.  Abstract Viewer/Itinerary Planner. San Diego, CA: Society for Neuroscience (Poster).  2010. 

Houlihan P, Dickey A, Merrill R, Strack S, Usachev Y.  Phosphoregulation of mitochondrial architecture and excitotoxicity in hippocampal neurons.  Abstract Viewer/Itinerary Planner. San Diego, CA: Society for Neuroscience (Poster).  2010. 

Kim M, Usachev Y.  Mitochondrial Ca2+ cycling facilitates activation of the transcription factor NFAT in sensory neurons.  J Neurosci.  2009 September 30. 29(39):12101-12114.
[Link]

Medvedeva Y, Kim M, Schnizler K, Usachev Y.  Functional tetrodotoxin-resistant Na(+) channels are expressed presynaptically in rat dorsal root ganglia neurons.  Neuroscience.  2009 March 17. 159(2):559-569.
[Link]

Houlihan P, Slupe A, Yorek M, Usachev Y.  Mechanisms of Ca2+ and electrical oscillations induced by minimal activation of TRPM8 in a subset of DRG neurons.  Abstract Viewer/Itinerary Planner. Chicago, IL: Society for Neuroscience (Poster)..  2009. 

Kim M, Usachev Y.  NGF activates NFAT-dependent transcription via the PI3K-Akt-GSK3b pathway in rat sensory neurons.  FASEB J.  2009. 23(1):884.1.

Kim M, Usachev Y.  NGF facilitates depolarization-induced NFAT activation via the PI3K-Akt-GSK3b pathway in DRG sensory neurons.  Abstract Viewer/Itinerary Planner. Chicago, IL: Society for Neuroscience (Poster)..  2009. 

Merrill R, Dagda R, Cribbs J, Green S, Usachev Y, Strack S.  PKA/AKAP1 inhibits fission via Drp1 to promote neuronal survival.  Abstract Viewer/Itinerary Planner. Chicago, IL: Society for Neuroscience (Poster)..  2009. 

Dagda R, Merrill R, Cribbs J, Chen Y, Hell J, Usachev Y, Strack S.  The spinocerebellar ataxia 12 gene product and protein phosphatase 2A regulatory subunit Bbeta2 antagonizes neuronal survival by promoting mitochondrial fission.  J Biol Chem.  2008 December 26. 283(52):36241-36248.
[Link]

Lu Y, Zhang M, Lim I, Hall D, Allen M, Medvedeva Y, McKnight G, Usachev Y, Hell J.  AKAP150-anchored PKA activity is important for LTD during its induction phase.  J Physiol.  2008 September 1. 586(Pt 17):4155-4164.
[Link]

Medvedeva Y, Kim M, Usachev Y.  Mechanisms of prolonged presynaptic Ca2+ signaling and glutamate release induced by TRPV1 activation in rat sensory neurons.  J Neurosci.  2008 May 14. 28(20):5295-5311.
[Link]

Schnizler K, Shutov L, Van Kanegan M, Merrill M, Nichols B, McKnight G, Strack S, Hell J, Usachev Y.  Protein kinase A anchoring via AKAP150 is essential for TRPV1 modulation by forskolin and prostaglandin E2 in mouse sensory neurons.  J Neurosci.  2008 May 7. 28(19):4904-4917.
[Link]

Medvedeva Y, Kim M, Schnizler K, Usachev Y.  Functional tetrodotoxin-resistant Na+ channels are expressed presynaptically in rat DRG neurons.  Neuroscience.  2008 March 17. 159(2):559-569.
[Link]

Usacheva M, Teichert M, Usachev Y, Sievert C, Biel M.  Interaction of the photobactericides methylene blue and toluidine blue with a fluorophore in Pseudomonas Aeruginosa cells.  Lasers in Surgery and Medicine.  2008. 40(1):55-61.
[Link]

Lu Y, Allen M, Halt A, Weisenhaus M, Dallapiazza R, Hall D, Usachev Y, McKnight S, Hell J.  Age-dependent requirement of AKAP150-anchored PKA and GluR2-lacking AMPA receptors in LTP.  EMBO J.  2007 November 28. 26(23):4879-4890.
[Link]

Jackson J, Usachev Y, Thayer S.  Bradykinin-induced NFAT-dependent transcription in rat dorsal root ganglion neurons.  Mol. Pharmacology.  2007 August. 72(2):303-310.
[Link]

Schnizler K, Van Kanegan M, Merrill M, McKnight S, Strack S, Hell J, Usachev Y.  Anchoring of PKA via AKAP150 is essential for TRPV1 modulation by forskolin and prostaglandin E2 in mouse DRG neurons.  2007 Abstract Viewer/Itinerary Planner. San Diego, CA: Society for Neuroscience (Poster).  2007. 

Usachev Y, Marsh A, Johanns T, Lemke M, Thayer S.  Activation of protein kinase C in sensory neurons accelerates Ca2+ uptake into the endoplasmic reticulum.  J of Neurosci.  2006. 26(1):311-318.
[Link]

Medvedeva Y, Usachev Y.  Functional Expression of Presynaptic Tetrodotoxin-Resistant Sodium Channels in Rat Sensory Neurons.  Abstract Viewer/Itinerary Planner. Atlanta, GA: Society for Neuroscience (Poster).  2006. 

Kim M, Thayer S, Usachev Y.  Mitochondrial Regulate Activation of the Transcription Factor NFAT in DRG Neurons.  Abstract Viewer/Itinerary Planner. Atlanta, GA: Society for Neuroscience (Poster).  2006. 

Strack S, Dagda R, cribbs J, Chen Y, Hell J, Green S, Usachev Y.  Outer Mitochondrial PP2A and PKA Control Neuronal Survival Through Mitochondrial Restructuring.  Abstract Viewer/Itinerary Planner. Atlanta, GA: Society for Neuroscience (Slide Session).  2006. 

Dagda R, Usachev Y, Strack S.  Dynamic regulation of mitochondrial morphology, calcium buffering, and neuronal survival by a neuron-specific protein phosphatase 2A holoenzyme.  Abstract Viewer/Itinerary Planner. Washington, DC: Society for Neuroscience (Poster).  2005. 

Kim M, Thayer S, Smirnov D, Usachev Y.  Mitochondrial Ca2+ cycling facilitates activation of the transcription factor NFAT in sensory neurons.  Abstract Viewer/Itinerary Planner. Washington, DC: Society for Neuroscience.  2005. 

Medvedeva Y, Usachev Y.  Vanilloid-induced presynaptic Ca2+ signaling and glutamate release in rat sensory neurons: The role of mitochondria.  Abstract Viewer/Itinerary Planner. Washington, DC: Society for Neuroscience.  2005. 

Usachev Y, Johanns T, Lemke M, Thayer S.  Activation of protein kinase C in sensory neurons accelerates calcium uptake into the endoplasmic reticulum.  Abstract Viewer/Itinerary Planner. Washington, DC: Society for Neuroscience.  2004. 

Medvedeva Y, Usachev Y.  Mitochondrial calcium cycling in sensory axons controls long-lasting synaptic activity induced by vanilloids.  Abstract Viewer/Itinerary Planner. Washington, DC: Society for Neuroscience.  2004. 

Usachev Y, DeMarco S, Campbell C, Strehler E, Thayer S.  Bradykinin and ATP accelerate Ca2+ efflux from rat sensory neurons via protein kinase C and the plasma membrane Ca2+ pump isoform 4.  Neuron.  2002. 33(1):113-122.
[Link]

Thayer S, Usachev Y, Pottorf W.  Modulating Ca2+ clearance from neurons (invited review).  Frontiers in Bioscience.  2002. 7:1255-1279.

Garcia M, Usachev Y, Thayer S, Strehler E, Windenbank A.  The plasma membrane ATPase plays a role in reducing Ca2+ mediated cytotoxicity in PC12 cells.  J Neuroscience Research.  2001 June 15. 64(6):661-669.
[PubMed]

Usachev Y, DeMarco S, Campbell C, Strehler E, Thayer S.  Bradykinin and ATP accelerate Ca2+ efflux from sensory neurons: the role of protein kinase C and the plasma membrane Ca2+ pump isoform 4.  Society for Neuroscience Abstracts.  2001. 27:Program No. 44.5.

Usachev Y, Toutenhoofd S, Goellner G, Strehler E, Thayer S.  Differentiation induces upregulation of plasma membrane Ca2+ -ATPase and concomitant increase in Ca2+ efflux in human neuroblastoma cell line IMR-32.  J Neurochemistry.  2001. 76(6):1756-1765.
[Link]

Usachev Y, Khammanivong A, Campbell C, Thayer S.  Particle-mediated gene transfer to rat neurons in primary culture. .  Pflugers Archiv.  2000. 439(6):730-738.
[PubMed]

Usachev Y, Thayer S.  Ca2+ influx in resting rat sensory neurons that regulates and is regulated by ryanodine-sensitive Ca2+ stores.  J of Physiology.  1999 August 15. 519 (pt. 1):115-130.
[Link]

Usachev Y, Thayer S.  Controlling the urge for a Ca2+ surge: all-or-none calcium release in neurons (invited review).  BioEssays.  1999. 21:743-750.

Usachev Y, Khammanivong A, Strehler E, Thayer S.  Modulation of Ca2+ efflux from cultured rat dorsal root ganglion (DRG) neurons by protein kinase C.  Society for Neuroscience Abstracts.  1999. 25:1191.

Usacheva M, Usachev Y, Teichert M, Biel M.  The role of methylene blue and toluidine blue monomers and dimers in inactivation bacteria.  Photochemistry and Photobiology.  1999. 69:565.

Usachev Y, Thayer S.  Co-transfection of primary neurons using particle-mediated gene delivery.  Society for Neuroscience Abstracts.  1998. 24:72.

Thayer S, Usachev Y, Werth J, Baron K.  Modulation of Ca2+ signaling in cultured rat dorsal root ganglion neurones.  J. of Physiology .  1998. 

Usachev Y, Thayer S.  All-or-none Ca2+ release from intracellular stores triggered by Ca2+ influx through voltage-gated Ca2+ channels in rat sensory neurons.  J Neuroscience.  1997 October 1. 17(19):7404-7414.
[Link]

Usachev Y, Thayer S.  The mechanism of refilling ryanodine-sensitive Ca2+ stores in rat sensory neurons.  Society for Neuroscience Abstracts .  1997. 23:1192.

Usachev Y, Thayer S.  All-or-none Ca2+ release from intracellular Ca2+ stores in rat DRG neurons.  Society for Neuroscience Abstracts.  1996. 22:340.

Werth J, Usachev Y, Thayer S.  Modulation of Ca2+ efflux from cultured rat DRG neurons.  J Neuroscience.  1996. 16(3):1008-1015.
[Link]

Usachev Y, Marchenko S, Sage S.  Cytosolic calcium concentration in resting and stimulated endothelium of excised intact rat aorta.  J Physiology.  1995 December 1. 489(pt. 2):309-317.
[Link]

Usachev Y, Kostyuk P, Verkhratsky A.  3-Isobutyl-1-methylxanthine (IBMX) affects potassium permeability in rat sensory neurones via pathways that are sensitive and insensitive to [Ca2+]in.  Pflugers Archiv.  1995 July. 430(3):420-428.
[PubMed]

Usachev Y, Verkhratsky A.  IBMX induces calcium release from intracellular stores in rat sensory neurons.  Cell Calcium.  1995 March. 17(3):197-206.
[Link]

Usachev Y, Marchenko S, Sage S.  Agonist-evoked changes in cytosolic calcium concentration in the endothelium of excised intact rat aorta.  J. of Physiology .  1995. 

Usachev Y, Verkhratsky A.  IBMX induces Ca2+ release from internal stores and affects K+ channels in isolated rat sensory neurones.  J. of Physiology .  1995. 

Shmigol A, Usachev Y, Kirischuk S, Kostyuk P, Verkhratsky A.  Properties of the caffeine-sensitive Ca2+ stores in mammalian neurons.  Neurophysiology.  1994. 26:16-24.

Usachev Y, Shmigol A, Pronchuk N, Verkhratsky A.  The role of caffeine-sensitive calcium stores in modulation of calcium signals in rat sensory neurons..  Proceedings of Russian Academy of Sciences.  1994. 334:381-384.

Usachev Y, Shmigol A, Pronchuk N, Kostyuk P, Verkhratsky A.  Caffeine-induced calcium release from internal stores in cultured rat sensory neurons.  Neuroscience.  1993 December. 57(3):845-859.
[Link]

Mironov S, Usachev Y, Lux H.  Spatial and temporal control of intracellular Ca dynamics in chick DRG neurons.  Pflugers Archiv .  1993 July. 424(2):183-191.
[PubMed]

Mironov S, Usachev Y.  Caffeine affects Ca uptake and Ca release from intracellular stores: fura-2 measurements in isolated snail neurons.  Neuroscience Letters.  1991. 123:200-202.

Usachev Y, Mironov S.  Effect of caffeine on intracellular Ca regulation processes in isolated snail neurons.  Neurophysiology.  1991. 23:66-73.

Mironov S, Usachev Y.  Sr and Ba transients in isolated snail neurons studied with fura-2. The recovery from depolarization induced load and modulation of Ca release from intracellular stores.  Neuroscience Letters.  1990. 112:184-189.

Usachev Y, Mironov S.  Effect of Sr and Ba ions on Ca binding and transport in nerve cells.  Neurophysiology.  1989. 21:820-825.

Shutov L, Usachev Y.  Mitochondria and PMCA regulate presynaptic [Ca2+]i in sensory neurons.  IASP 14th World Congress on Pain (Poster), Milan, Italy. 

Usachev Y.  Mitochondrial Ca2+ transport in the control of neuronal plasticity and survival: molecular and cellular mechanisms.  V.K. Gribkoff and L.K. Kaczmarek, Series Editors. 

Usachev Y, Mohapatra D.  Modulation of voltage-gated Na+ and K+ channels in inflammatory and neuropathic pain.  T.J. Price and G. Dussor; Elsevier. 

 .  Techniques to Investigate Neuronal Mitochondrial Function.  formerly published by Humana Press. 

Date Last Modified: 06/07/2014 - 21:56:23