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.)

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 Neurons Alters Behavioral Effects of Cocaine in Mice. Neuropsychopharmacology. 2016 Jul 29;.

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 Mar 16;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 Feb 16;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 Aug;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 Jun 2;112(22):7091-6.

de Velasco, Ezequiel Marron Fernandez, McCall NM, and Wickman K. "GIRK Channel Plasticity and Implications for Drug Addiction." International Review of Neurobiology (2015).

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 May 6;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 Sep;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 Sep;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 Jul 22;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 Jan;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. doi: 10.1515/revneuro-2012-0045. PubMed PMID: 22944653.

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 Aug 24;31(34):12251-7. PubMed PMID: 21865468; PubMed Central PMCID: PMC3174781.

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 Aug 11;71(3):488-97. PubMed PMID: 21835345; PubMed Central PMCID: PMC3184528.

Posokhova E, Wydeven N, Allen KL, Wickman K, Martemyanov KA. RGS6/Gß5 complex accelerates IKACh gating kinetics in atrial myocytes and modulates
parasympathetic regulation of heart rate. Circ Res. 2010 Nov 26;107(11):1350-4. Epub 2010 Sep 30. Erratum in: Circ Res. 2011 Feb 4;108(3):e3. PubMed PMID: 20884879; PubMed Central PMCID: PMC3014848.

Arora D, Haluk DM, Kourrich S, Pravetoni M, Fernandez-Alacid L, Nicolau JC, Lujan R, Wickman K. Altered neurotransmission in the mesolimbic reward system of Girk mice. J Neurochem. 2010 Sep 1;114(5):1487-97. Epub 2010 Jun 16. PubMed PMID: 20557431; PubMed Central PMCID: PMC2941778.

Xie K, Allen KL, Kourrich S, Colan-Saez J, Thomas MJ, Wickman K, Martemyanov KA. Gbeta5 recruits R7 RGS proteins to GIRK channels to regulate the timing of neuronal inhibitory signaling. Nat Neurosci. 2010 Jun;13(6):661-3. Epub 2010 May 9. PubMed PMID: 20453851; PubMed Central PMCID: PMC2876203.

Kozell LB, Walter NA, Milner LC, Wickman K, Buck KJ. Mapping a barbiturate withdrawal locus to a 0.44 Mb interval and analysis of a novel null mutant identify a role for Kcnj9 (GIRK3) in withdrawal from pentobarbital, zolpidem, and ethanol. J Neurosci. 2009 Sep 16;29(37):11662-73. PubMed PMID: 19759313; PubMed Central PMCID: PMC2813520.

Perry CA, Pravetoni M, Teske JA, Aguado C, Erickson DJ, Medrano JF, Lujan R, Kotz CM, Wickman K. Predisposition to late-onset obesity in GIRK4 knockout mice. Proc Natl Acad Sci U S A. 2008 Jun 10;105(23):8148-53. Epub 2008 Jun 3. PubMed PMID: 18523006; PubMed Central PMCID: PMC2430374.

Cruz HG, Berton F, Sollini M, Blanchet C, Pravetoni M, Wickman K, Lascher C. Absence and rescue of morphine withdrawal in GIRK/Kir3 knock-out mice. J Neurosci. 2008 Apr 9;28(15):4069-77. PubMed PMID: 18400906.

Anderson GR, Cao Y, Davidson S, Truong HV, Pravetoni M, Thomas MJ, Wickman K, Giesler GJ Jr, Martemyanov KA. R7BP complexes with RGS9-2 and RGS7 in the striatum differentially control motor learning and locomotor responses to cocaine. Neuropsychopharmacology. 2010 Mar;35(4):1040-50. Epub 2009 Dec 30. PubMed PMID: 20043004; PubMed Central PMCID: PMC2887292.

Anderson GR, Cao Y, Davidson S, Truong HV, Pravetoni M, Thomas MJ, Wickman K, Giesler GJ Jr, Martemyanov KA. R7BP complexes with RGS9-2 and RGS7 in the striatum differentially control motor learning and locomotor responses to cocaine. Neuropsychopharmacology. 2010 Mar;35(4):1040-50. Epub 2009 Dec 30.

Haluk DM, Wickman K. Evaluation of study design variables and their impact on food-maintained operant responding in mice. Behav Brain Res. 2010 Mar 5;207(2):394-401. Epub 2009 Oct 29.

Pravetoni M, Wickman K. Behavioral characterization of mice lacking GIRK/Kir3 channel subunits. Genes Brain Behav. 2008 Jan 12.

Current Graduate Students:

Nora McCall (Neuroscience, University of Minnesota)

Kevin Wickman