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The Journal of Neuroscience, August 24, 2005, 25(34):7801-7804; doi:10.1523/JNEUROSCI.1699-05.2005

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BRIEF COMMUNICATION
G-Protein-Gated Potassium (GIRK) Channels Containing the GIRK2 Subunit Are Control Hubs for Pharmacologically Induced Hypothermic Responses

Alberto C. S. Costa,^1,2 Melissa R. Stasko,¹ Markus Stoffel,³ and Jonah J. Scott-McKean¹

¹Eleanor Roosevelt Institute, University of Denver, Denver, Colorado 80206, ²Department of Psychiatry, University of Colorado Health Science Center, Denver, Colorado 80262, and ³Laboratory of Metabolic Diseases, Rockefeller University, New York, New York 10021

Hypothermic responses of rodents to the peripheral or intraventricular injection of many individual neurotransmitter receptor agonists have been well documented. Because many hypothermia-inducing agonists are also known to activate G-protein-gated potassium (GIRK) channels, we investigated the hypothermic response to several of these agents on Girk2 null mutant mice. Core body temperatures were measured through radiotelemetry, and animals were maintained in special temperature-regulated chambers to ensure the accuracy of the measurements. The resulting data indicate that the activation of GIRK2-containing potassium channels plays a significant role in hypothermia induced by the activation of serotonergic (5-HT_1A), GABAergic (GABA_B), muscarinic (m₂), adenosine (A₁), and µ, , and opioid receptors. These channels also are involved in the alcohol-induced hypothermic response. These results have implications for the understanding of pharmacologically induced hypothermia and thermoregulatory mechanisms.

Key words: hypothermia; GPCR; 5-HT_1A receptor; GABA_B receptor; muscarinic; dopaminergic; adrenergic; adenosine; opioid; alcohol; potassium channels; Down syndrome

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Received April 28, 2005; revised July 15, 2005; accepted July 19, 2005.

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