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The Journal of Neuroscience, August 1, 2000, 20(15):5608-5615

Brain Localization and Behavioral Impact of the G-Protein-Gated K⁺ Channel Subunit GIRK4

Kevin Wickman¹, Christine Karschin², Andreas Karschin², Marina R. Picciotto³, and David E. Clapham⁴

¹ Department of Pharmacology, University of Minnesota Minneapolis, Minnesota, ² Max-Planck-Institute for Biophysical Chemistry, Molecular Neurobiology of Signal Transduction, Göttingen, Germany, ³ Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, and ⁴ Howard Hughes Medical Institute, Departments of Neurobiology and Cardiology, Harvard Medical School/Children's Hospital, Boston, Massachusetts 02115

Neuronal G-protein-gated potassium (K_G) channels are activated by several neurotransmitters and constitute an important mode of synaptic inhibition in the mammalian nervous system. K_G channels are composed of combinations of four subunits termed G protein-gated inwardly rectifying K⁺ channels (GIRK). All four GIRK subunits are expressed in the brain, and there is a general consensus concerning the expression patterns of GIRK1, GIRK2, and GIRK3. The localization pattern of GIRK4, however, remains controversial. In this study, we exploit the negative background of mice lacking a functional GIRK4 gene to identify neuronal populations that contain GIRK4 mRNA. GIRK4 mRNA was detected in only a few regions of the mouse brain, including the deep cortical pyramidal neurons, the endopiriform nucleus and claustrum of the insular cortex, the globus pallidus, the ventromedial hypothalamic nucleus, parafascicular and paraventricular thalamic nuclei, and a few brainstem nuclei (e.g., the inferior olive and vestibular nuclei). Mice lacking GIRK4 were viable and appeared normal and did not display gross deficiencies in locomotor activity, visual tasks, and pain perception. Furthermore, GIRK4-deficient mice performed similarly to wild-type controls in the passive avoidance paradigm, a test of aversive learning. GIRK4 knock-out mice did, however, exhibit impaired performance in the Morris water maze, a test of spatial learning and memory.

Key words: potassium channel; G-protein; GIRK; Kir3.0; in situ hybridization; Morris water maze; passive avoidance; locomotor activity; mice

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Copyright © 2000 Society for Neuroscience  0270-6474/00/20155608-08$05.00/0

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