Kevin D. Wickman, Ph.D.

Professor, Department of Pharmacology

E-MAIL: wickm002@umn.edu

Lab: http://wickmanlab.phcl.umn.edu/index.html

Research Interests:

My lab studies mechanisms controlling the excitability of cells in the brain and heart. Dysregulation of cell excitability contributes to many debilitating and/or life-threatening medical conditions, including cardiac arrhythmias, epilepsy, anxiety, depression, schizophrenia, Down Syndrome, addiction, and pain. We seek to better understand mechanisms that control cell excitability, so that safer and more effective strategies can be developed to treat these afflictions.  

Research projects in my lab use state-of-the-art techniques and approaches including slice electrophysiology, traditional and conditional gene knockout/knockdown, chemogenetics (DREADDs), intracranial manipulations, and electrocardiogram telemetry, as well as behavioral assessments of reward, mood, cognition, and nociception. While these approaches can be flexibly adapted to investigate the contribution any molecular target to organ function or behavior, our recent work has focused on the G protein-gated inwardly-rectifying potassium channel, or GIRK channel.  

GIRK channels mediate the impact of the parasympathetic nervous system on heart rate and arrhythmogenesis. They also play key roles in pain perception, addiction, cognition, and mood. Our ongoing funded projects are directed at identifying molecules and mechanisms that modulate GIRK channel activity in neurons and cardiac myocytes, elucidating roles for GIRK channels in mood-related behavior and cognition, understanding experience- and drug-induced plasticity of GIRK-dependent signaling in the context of addiction, and evaluating the efficacy of novel small-molecular modulators of GIRK channels in preclinical studies of mood, pain, and cognitive dysfunction.


Selected Publications:

(For a comprehensive list of recent publications, refer to PubMed, a service provided by the National Library of Medicine.)

  • Anderson A, Kulkarni K, Marron Fernandez de Velasco E, Carlblom N, Xia Z, Nakano A, Martemyanov KA, Tolkacheva EG, Wickman K. Expression and relevance of the G protein-gated K+ channel in the mouse ventricle. Sci Rep. 2018 Jan 19;8(1):1192.
  • Luján R, Aguado C, Ciruela F, Cózar J, Kleindienst D, de la Ossa L, Bettler B, Wickman K, Watanabe M, Shigemoto R, Fukazawa Y. Differential association of GABAB receptors with their effector ion channels in Purkinje cells. Brain Struct Funct. 2017 Nov 25. doi: 10.1007/s00429-017-1568-y.
  • Wieting JM, Vadukoot AK, Sharma S, Abney KK, Bridges TM, Daniels JS, Morrison RD, Wickman K, Weaver CD, Hopkins CR. Discovery and characterization of 1H-pyrazol-5-yl-2-phenylacetamides as novel, non-urea-containing GIRK1/2 potassium channel activators. ACS Chem Neurosci. 2017;8(9):1873-1879.
  • Marron Fernandez de Velasco E, Zhang L, N Vo B, Tipps M, Farris S, Xia Z, Anderson A, Carlblom N, Weaver CD, Dudek SM, Wickman K. GIRK2 splice variants and neuronal G protein-gated K+ channels: implications for channel function and behavior. Sci Rep. 2017 May 9;7(1):1639.
  • Marron Fernandez de Velasco E, Carlblom N, Xia Z, Wickman K. Suppression of inhibitory G protein signaling in forebrain pyramidal neurons triggers plasticity of glutamatergic neurotransmission in the nucleus accumbens core. Neuropharmacology. 2017;117:33-40.
  • McCall NM, Kotecki L, Dominguez-Lopez S, de Velasco EM, Carlblom N, Sharpe AL, Beckstead MJ, Wickman K. Selective ablation of GIRK channels in dopamine nneurons alters behavioral effects of cocaine in mice.  Neuropsychopharmacology. 2017;42(3):707-715.
  • Munoz MB, Padgett CL, Rifkin R, Terunuma M, Wickman K, Contet C, Moss SJ, Slesinger PA. A Role for the GIRK3 subunit in methamphetamine-induced attenuation of GABAB receptor-activated GIRK currents in VTA dopamine Neurons. J Neurosci. 2016;36(11):3106-14.
  • Mesirca P, Bidaud I, Briec F, Evain S, Torrente AG, Le Quang K, Leoni AL, Baudot M, Marger L, Chung You Chong A, Nargeot J, Striessnig J, Wickman K, Charpentier F, Mangoni ME. G protein-gated IKACh channels as therapeutic targets for treatment of sick sinus syndrome and heart block. Proc Natl Acad Sci U S A. 2016;113(7):E932-41.
  • Marron Fernandez de Velasco E, Hearing M, Xia Z, Victoria NC, Luján R, Wickman K. Sex differences in GABABR-GIRK signaling in layer 5/6 pyramidal neurons of the mouse prelimbic cortex. Neuropharmacology. 2015;95:353-60.
  • Herman MA, Sidhu H, Stouffer DG, Kreifeldt M, Le D, Cates-Gatto C, Munoz MB, Roberts AJ, Parsons LH, Roberto M, Wickman K, Slesinger PA, Contet C. GIRK3 gates activation of the mesolimbic dopaminergic pathway by ethanol. Proc Natl Acad Sci U S A. 2015;112(22):7091-6.
  • dMarron Fernandez de Velasco E, McCall N, Wickman K. GIRK channel plasticity and implications for drug addiction. Int Rev Neurobiol. 2015;123:201-38.
  • Kotecki L, Hearing M, McCall NM, Marron Fernandez de Velasco E, Pravetoni M, Arora D, Victoria NC, Munoz MB, Xia Z, Slesinger PA, Weaver CD, Wickman K. GIRK channels modulate opioid-induced motor activity in a cell type- and subunit-dependent manner. J Neurosci. 2015;35(18):7131-42.
  • Krogh KA, Wydeven N, Wickman K, Thayer SA. HIV-1 protein Tat produces biphasic changes in NMDA-evoked increases in intracellular Ca2+ concentration via activation of Src kinase and nitric oxide signaling pathways. J Neurochem. 2014;130(5):642-56.
  • Krogh KA, Wydeven N, Wickman K, Thayer SA. HIV-1 protein Tat produces biphasic changes in NMDA-evoked increases in intracellular Ca2+ concentration via activation of Src kinase and nitric oxide signaling pathways. J Neurochem. 2014;130(5):642-56.
  • Mesirca P, Alig J, Torrente AG, Müller JC, Marger L, Rollin A, Marquilly C, Vincent A, Dubel S, Bidaud I, Fernandez A, Seniuk A, Engeland B, Singh J, Miquerol L, Ehmke H, Eschenhagen T, Nargeot J, Wickman K, Isbrandt D, Mangoni ME. Cardiac arrhythmia induced by genetic silencing of 'funny' (f) channels is rescued by GIRK4 inactivation. Nat Commun. 2014 Aug 21;5:4664.
  • Wydeven N, Marron Fernandez de Velasco E, Du Y, Benneyworth MA, Hearing MC, Fischer RA, Thomas MJ, Weaver CD, Wickman K. Mechanisms underlying the activation of G-protein-gated inwardly rectifying K+ (GIRK) channels by the novel anxiolytic drug, ML297. Proc Natl Acad Sci U S A. 2014;111(29):10755-60.
  • Luján R, Marron Fernandez de Velasco E, Aguado C, Wickman K. New insights into the therapeutic potential of Girk channels. Trends Neurosci. 2014;37(1):20-9.
  • Hearing MC, Zink AN, Wickman K. Cocaine-induced adaptations in metabotropic inhibitory signaling in the mesocorticolimbic system. Rev Neurosci. 2012;23(4):325-51.
  • Arora D, Hearing M, Haluk DM, Mirkovic K, Fajardo-Serrano A, Wessendorf MW, Watanabe M, Lujan R, Wickman K. Acute cocaine exposure weakens GABA(B) receptor-dependent G-protein-gated inwardly rectifying K+ signaling in dopamine neurons of the ventral tegmental area. J Neurosci. 2011;31:12251-7.
  • Sohn JW, Xu Y, Jones JE, Wickman K, Williams KW, Elmquist JK. Serotonin 2C receptor activates a distinct population of arcuate pro-opiomelanocortin neurons via TRPC channels. Neuron. 2011;71(3):488-97.

Current Graduate Students:

Margot DeBaker (Neuroscience, University of Minnesota)

Nora McCall (Neuroscience, University of Minnesota)

Kevin Wickman