Effects of genetic deletion of the Kv4.2 voltage-gated potassium channel on murine anxiety-, fear- and stress-related behaviors

Laboratory of Behavioral and Genomic Neuroscience, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD, USA. .
Biology of Mood and Anxiety Disorders 03/2012; 2(1):5. DOI: 10.1186/2045-5380-2-5
Source: PubMed


Potassium channels have been proposed to play a role in mechanisms of neural plasticity, and the Kv4.2 subunit has been implicated in the regulation of action-potential back-propagation to the dendrites. Alterations in mechanisms of plasticity have been further proposed to underlie various psychiatric disorders, but the role of Kv4.2 in anxiety or depression is not well understood.
In this paper, we analyzed the phenotype Kv4.2 knockout mice based on their neurological function, on a battery of behaviors including those related to anxiety and depression, and on plasticity-related learning tasks.
We found a novelty-induced hyperactive phenotype in knockout mice, and these mice also displayed increased reactivity to novel stimulus such as an auditory tone. No clear anxiety- or depression-related phenotype was observed, nor any alterations in learning/plasticity-based paradigms.
We did not find clear evidence for an involvement of Kv4.2 in neuropsychiatric or plasticity-related phenotypes, but there was support for a role in Kv4.2 in dampening excitatory responses to novel stimuli.

Download full-text


Available from: Dax A Hoffman, Oct 05, 2015
11 Reads
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Voltage-gated ion channels are important mediators of physiological functions in the central nervous system. The cyclic activation of these channels influences neurotransmitter release, neuron excitability, gene transcription, and plasticity, providing distinct brain areas with unique physiological and pharmacological response. A growing body of data has implicated ion channels in the susceptibility or pathogenesis of psychiatric diseases. Indeed, population studies support the association of polymorphisms in calcium and potassium channels with the genetic risk for bipolar disorders (BPDs) or schizophrenia. Moreover, point mutations in calcium, sodium, and potassium channel genes have been identified in some childhood developmental disorders. Finally, antibodies against potassium channel complexes occur in a series of autoimmune psychiatric diseases. Here we report recent studies assessing the role of calcium, sodium, and potassium channels in BPD, schizophrenia, and autism spectrum disorders, and briefly summarize promising pharmacological strategies targeted on ion channels for the therapy of mental illness and related genetic tests.
    Frontiers in Genetics 05/2013; 4:76. DOI:10.3389/fgene.2013.00076
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The striatum, major input structure of basal ganglia, integrates glutamatergic cortical and thalamic input to control psychomotor behaviors. Nigrostriatal dopamine (DA) neurodegeneration in Parkinson's disease causes a profound loss of spines and glutamatergic synapses in the striatal medium spiny neurons (MSN). Adaptive responses, a form of homeostatic plasticity, to these changes are found by a decrease of a potassium Kv4 channel-dependent inactivating A-type potassium (KIA) current that increases MSNs intrinsic excitability. Nevertheless, the functional outcome of these compensatory mechanisms does not allow adequate behavioral recovery in vivo. We thus addressed the question of whether further blockade of Kv4 activity could enhance the striatal responsiveness of MSNs to the DA depletion and restore normal function in vivo. To test this hypothesis, we examined the effects of a selective blocker of Kv4 channels, AmmTX3, on the motor, cognitive and emotional symptoms produced by 6- hydroxydopamine (6-OHDA) lesions of the nigrostriatal DA pathway in rats. Striatal infusion of AmmTX3 (0.2-0.4 µg) reduced motor deficits, decreased anxiety and restored short-term social and spatial memories. These results underlie the importance of Kv4 channels as players of the homeostatic responses, and, more importantly, provides a potential target for adjunctive therapies for Parkinson's disease.
    Behavioural Pharmacology 09/2014; 26(1-2). DOI:10.1097/FBP.0000000000000107 · 2.15 Impact Factor