G-protein-gated potassium (GIRK) channels containing the GIRK2 subunit are control hubs for pharmacologically induced hypothermic responses.
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 mu, delta, and kappa 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.
Costa
Alberto C S
AC
Eleanor Roosevelt Institute, University of Denver, Denver, Colorado 80206, USA. acosta@du.edu
Stasko
Melissa R
MR
Stoffel
Markus
M
Scott-McKean
Jonah J
JJ
D000818:Animals; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000819:agonists* / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007036:Hypothermia, Induced / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C497069:Kcnj6 protein, mouse; D017366:Serotonin Receptor Agonists