A long-standing interest of our lab has been the G protein-gated inwardly-rectifying potassium/K+ channel, or GIRK channel. GIRK channels are key determinant of excitability in the heart and central nervous system. GIRK channels expressed in the heart mediate the impact of the parasympathetic nervous system on heart rate and rhythm. GIRK channels expressed in neurons have been implicated in addiction- and mood-related behaviors, learning and memory, pain perception, and opioid analgesia. Our ongoing work seeks to characterize and exploit the molecular diversity within the GIRK channel family, identify factors that modulate GIRK channel activity, evaluate the contributions made by GIRK channels to organ physiology and behavior, and understand how experience alters the strength of GIRK-dependent signaling. If we can understand how experience drives the plasticity of GIRK-dependent signaling, and the implications of GIRK channel activity to behavior, we may be able to prevent or reverse adaptations that underlie neurological disorders such as anxiety, addiction, and pain. The recent development and characterization of small-molecule modulators of defined GIRK channel subtypes affords opportunities to explore translational applications for our pre-clinical efforts. Please check out some of our recent publications:

Ethanol-Induced Suppression of G Protein-Gated Inwardly Rectifying K+-Dependent Signaling in the Basal Amygdala. Marron Fernandez de Velasco E, Tipps ME, Haider B, Souders A, Aguado C, Rose TR, Vo BN, DeBaker MC, Lujan R, Wickman K. Biol Psychiatry. 2023 April (Online ahead of print).

RGS6 negatively regulates inhibitory G protein signaling in dopamine neurons and positively regulates binge-like alcohol consumption in mice. DeBaker MC, Mitten EH, Rose TR, Marron Fernandez de Velasco E, Gao R, Lee AM, Wickman K. Br J Pharmacol. 2023 Aug;180(16):2140-2155.

GIRK channel activity in prelimbic pyramidal neurons regulates the extinction of cocaine conditioned place preference in male mice. Rose TR, Marron Fernandez de Velasco E, Mitten EH, Wickman K. Addict Biol. 2023 Jan;28(1):e13256. .

Characterization of VU0468554, a new selective inhibitor of cardiac GIRK channels. Anderson A, Vo BN, Marron Fernandez de Velasco E, Hopkins CR, Weaver CD, Wickman K. Molecular Pharmacology. 2021 Dec;100(6):540-547

Bidirectional influence of limbic GIRK channel activation on innate avoidance behavior. Vo BN, Marron Fernandez de Velasco E, Rose TR, Oberle H, Luo H, Hopkins CR, Wickman K. J Neurosci. 2021 May 24;41(27):5809-5821.

Differential Impact of Inhibitory G-Protein Signaling Pathways in Ventral Tegmental Area Dopamine Neurons on Behavioral Sensitivity to Cocaine and Morphine. DeBaker MC, Marron Fernandez de Velasco E, McCall NM, Lee AM, Wickman K. eNeuro. 2021 Mar 26;8(2)

Impact of Acute and Persistent Excitation of Prelimbic Pyramidal Neurons on Motor Activity and Trace Fear Learning. Rose TR, Marron Fernandez de Velasco E, Vo BN, Tipps ME, Wickman K. J Neurosci. 2021 Feb 3;41(5):960-971.

GPCR-dependent biasing of GIRK channel signaling dynamics by RGS6 in mouse sinoatrial nodal cells. Anderson A, Masuho I, Marron Fernandez de Velasco E, Nakano A, Birnbaumer L, Martemyanov, KA, Wickman K. PNAS. 2020 June 23;117(25):14522-14531.

GIRK channel activity in dopamine neurons of the ventral tegmental area bi-directionally regulates behavioral sensitivity to cocaine. McCall NM, Marron Fernandez de Velasco E, Wickman K. J Neurosci. 2019 May 8;39(19):3600-3610.

Inhibition of Pyramidal Neurons in the Basal Amygdala Promotes Fear Learning. Tipps M, Marron Fernandez de Velasco E, Schaeffer A, Wickman K. eNeuro. 2018 Oct 31;5(5).

Atrial GIRK Channels Mediate the Effects of Vagus Nerve Stimulation on Heart Rate Dynamics and Arrhythmogenesis. Lee SW, Anderson A, Guzman PA, Nakano A, Tolkacheva EG, Wickman K. Front Physiol. 2018 Jul 19;9:943.

Suppression of inhibitory G protein signaling in forebrain pyramidal neurons triggers plasticity of glutamatergic neurotransmission in the nucleus accumbens core. Marron Fernandez de Velasco E, Carlblom N, Xia Z, Wickman K. Neuropharmacology. 2017 May 1;117:33-40.

G Protein-Gated K+ Channel Ablation in Forebrain Pyramidal Neurons Selectively Impairs Fear Learning. Victoria NC, Marron Fernandez de Velasco E, Ostrovskaya O, Metzger S, Xia Z, Kotecki L, Benneyworth MA, Zink AN, Martemyanov KA, Wickman K. Biol Psychiatry. 2016 Nov 15;80(10):796-806.

Selective Ablation of GIRK Channels in Dopamine Neurons Alters Behavioral Effects of Cocaine in Mice. McCall NM, Kotecki L, Dominguez-Lopez S, Marron Fernandez de Velasco E, Carlblom N, Sharpe AL, Beckstead MJ, Wickman K. Neuropsychopharmacology. 2017 Feb;42(3):707-715.

GIRK Channels Modulate Opioid-Induced Motor Activity in a Cell Type- and Subunit-Dependent Manner. 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. J Neurosci. 2015 May 6;35(18):7131-42.

Mechanisms underlying the activation of G-protein-gated inwardly rectifying K+ (GIRK) channels by the novel anxiolytic drug, ML297. Wydeven N, Marron Fernandez de Velasco E, Du Y, Benneyworth MA, Hearing MC, Fischer RA, Thomas MJ, Weaver CD, Wickman K. Proc Natl Acad Sci U S A. 2014 Jul 22;111(29):10755-60

We are also utilizing powerful approaches in neuromodulation (chemogenetics and optogenetics) and in vivo recordings to understand the circuit and neuronal basis of complex behaviors. As part of this work, we have invested heavily in the development of viral vectors that can be used to sample and manipulate neuronal activity, in a brain region- and neuron-specific manner. Our investment prompted us to establish the University of Minnesota Viral Vector and Cloning Core, service core that offers a convenient and low-cost option for custom viral vector development and production to investigators at the University of Minnesota and elsewhere.

Complete listing of publications authored or co-authored by Dr. Wickman