Research Interests:

My laboratory studies neuronal and cardiac G protein-gated potassium (KG) channels found in the heart and nervous system. Many important hormones and neurotransmitters stimulate KG channel activity with profound effects on a diverse array of physiological processes such as heart rate regulation, learning and memory, locomotion, and sensory perception. In addition, KG function has been implicated in the effects of drugs of abuse such as heroine, cocaine, marijuana, and alcohol. Since G protein activation also leads to the modulation of several enzymes and other ion channels, it has been difficult to determine the contribution of KG function to a physiological effect. If we understood better the relative contributions of individual enzymes and ion channels to the physiological effects of neurotransmitters and drugs of abuse, it might be possible to design more effective therapeutic drugs.

Few pharmacological tools exist for studying KG channels, negating a line of research proven useful for localization, ultrastructural characterization and role identification for many enzymes ion channels. Genetic approaches, however, have proven useful in these regards. For example, we recently used a gene ablation strategy to demonstrate that the the cardiac G protein-gated potassium channel mediates a large portion of the heart rate slowing response to vagal nerve activation. Using a similar approach with the remaining subunits, we are beginning to understand the contribution of this channel class to pain perception and addiction.

Selected Publications:

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

Aguado C, Colón J, Ciruela F, Schlaudraff F, Cabañero MJ, Perry C, Watanabe M, Liss B, Wickman K, Luján R. Cell type-specific subunit composition of G protein-gated potassium channels in the cerebellum. J Neurochem. 2007 Dec 20.

Anderson GR, Lujan R, Semenov A, Pravetoni M, Posokhova EN, Song JH, Uversky V, Chen CK, Wickman K, Martemyanov KA. Expression and localization of RGS9-2/G 5/R7BP complex in vivo is set by dynamic control of its constitutive degradation by cellular cysteine proteases. J Neurosci. 2007 Dec 19;27(51):14117-27.

Labouèbe G, Lomazzi M, Cruz HG, Creton C, Luján R, Li M, Yanagawa Y, Obata K, Watanabe M, Wickman K, Boyer SB, Slesinger PA, Lüscher C. RGS2 modulates coupling between GABA(B) receptors and GIRK channels in dopamine neurons of the ventral tegmental area. Nat Neurosci. 2007 Dec;10(12):1559-68.

Marker CL, Lujan R, Colon J, Wickman K.   Distinct populations of spinal cord lamina II interneurons expressing G-protein-gated potassium channels. J Neurosci. 2006 Nov 22;26(47):12251-9.

Kulik A, Vida I, Fukazawa Y, Guetg N, Kasugai Y, Marker CL, Rigato F, Bettler B, Wickman K, Frotscher M, Shigemoto R. Compartment-dependent colocalization of Kir3.2-containing K+ channels and GABAB receptors in hippocampal pyramidal cells. J Neurosci. 2006 Apr 19;26(16):4289-97.