Increased motor drive and sleep loss in mice lacking Kv3-type potassium channels.
The voltage-gated potassium channels Kv3.1 and Kv3.3 are widely expressed in the brain, including areas implicated in the control of motor activity and in areas thought to regulate arousal states. Although Kv3.1 and Kv3.3-single mutants show some physiological changes, previous studies revealed relatively subtle behavioral alterations suggesting that Kv3.1 and Kv3.3 channel subunits may be encoded by a pair of redundant genes. In agreement with this hypothesis, Kv3.1/Kv3.3-deficient mice display a 'strong' mutant phenotype that includes motor dysfunction (ataxia, myoclonus, tremor) and hyperactivity when exposed to a novel environment. In this paper we report that Kv3.1/Kv3.3-deficient mice are also constitutively hyperactive. Compared to wildtype mice, double mutants display 'restlessness' that is particularly prominent during the light period, when mice are normally at rest, characterized by more than a doubling of ambulatory and stereotypic activity, and accompanied by a 40% sleep reduction. When we reinvestigated both single mutants, we observed constitutive increases of ambulatory and stereotypic activity in conjunction with sleep loss in Kv3.1-single mutants but not in Kv3.3-single mutants. These findings indicate that the absence of Kv3.1-channel subunits is primarily responsible for the increased motor drive and the reduction in sleep time.
Center for Basic Neuroscience and Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, Texas, USA.
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F
Espinosa
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G
Marks
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N
Heintz
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RH
Joho
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D006579:Heterozygote; D006720:Homozygote; D006948:Hyperkinesis / Q000150:complications / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology*; D009207:Myoclonus / Q000150:complications / Q000235:genetics / Q000503:physiopathology; D009479:Neuropeptides / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015221:Potassium Channels / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated / Q000172:deficiency* / Q000235:genetics; D051670:Shaw Potassium Channels; D012890:Sleep / Q000502:physiology*; D013239:Stereotyped Behavior / Q000502:physiology
C085724:Kcnc3 protein, mouse; D009479:Neuropeptides; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D051670:Shaw Potassium Channels