Genetic KCa3.1-Deficiency Produces Locomotor Hyperactivity and Alterations in Cerebral Monoamine Levels

Autor: Mithula Sivasaravanaparan, Maj Rabjerg, Heike Wulff, Ralf Köhler, Kate Lykke Lambertsen, Jan Bert Gramsbergen, Aida Oliván-Viguera, Nicholas Ditzel, Linda Sevelsted-Møller
Přispěvatelé: Dryer, Stuart E
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Mouse
Dopamine
lcsh:Medicine
Gene Expression
Cardiovascular
Biochemistry
Open field
Ion Channels
chemistry.chemical_compound
Norepinephrine
0302 clinical medicine
Catecholamines
Corticosterone
Monoaminergic
Molecular Cell Biology
lcsh:Science
Cerebral Cortex
0303 health sciences
Multidisciplinary
Behavior
Animal
Animal Models
Intermediate-Conductance Calcium-Activated Potassium Channels
3. Good health
medicine.anatomical_structure
Cerebral cortex
Neurological
Medicine
medicine.drug
Research Article
medicine.medical_specialty
Drugs and Devices
Serotonin
General Science & Technology
Hyperkinesis
Motor Activity
Cardiovascular Pharmacology
Molecular Genetics
03 medical and health sciences
Model Organisms
Neuropharmacology
Internal medicine
Behavioral and Social Science
medicine
Genetics
Animals
Gene Regulation
Benzothiazoles
Biology
030304 developmental biology
Behavior
Animal
Prevention
lcsh:R
Neurosciences
Proteins
Brain Disorders
Monoamine neurotransmitter
Endocrinology
chemistry
Cellular Neuroscience
Catecholamine
lcsh:Q
030217 neurology & neurosurgery
Neuroscience
Zdroj: PLoS ONE
Lambertsen, K L, Gramsbergen, J B, Sivasaravanaparan, M, Ditzel, N, Møller, L M S, Oliván-Viguera, A, Rabjerg, M, Wulff, H & Köhler, R 2012, ' Genetic KCa3.1-deficiency produces locomotor hyperactivity and alterations in cerebral monoamine levels ', P L o S One, vol. 7, no. 10, pp. e47744 . https://doi.org/10.1371/journal.pone.0047744
PloS one, vol 7, iss 10
PLoS ONE, Vol 7, Iss 10, p e47744 (2012)
ISSN: 1932-6203
Popis: Author(s): Lambertsen, Kate Lykke; Gramsbergen, Jan Bert; Sivasaravanaparan, Mithula; Ditzel, Nicholas; Sevelsted-Moller, Linda Maria; Olivan-Viguera, Aida; Rabjerg, Maj; Wulff, Heike; Kohler, Ralf | Abstract: BackgroundThe calmodulin/calcium-activated K(+) channel KCa3.1 is expressed in red and white blood cells, epithelia and endothelia, and possibly central and peripheral neurons. However, our knowledge about its contribution to neurological functions and behavior is incomplete. Here, we investigated whether genetic deficiency or pharmacological activation of KCa3.1 change behavior and cerebral monoamine levels in mice.Methodology/principal findingsIn the open field test, KCa3.1-deficiency increased horizontal activity, as KCa3.1(-/-) mice travelled longer distances (≈145% of KCa3.1(+/+)) and at higher speed (≈1.5-fold of KCa3.1(+/+)). Working memory in the Y-maze was reduced by KCa3.1-deficiency. Motor coordination on the rotarod and neuromuscular functions were unchanged. In KCa3.1(-/-) mice, HPLC analysis revealed that turn-over rates of serotonin were reduced in frontal cortex, striatum and brain stem, while noradrenalin turn-over rates were increased in the frontal cortex. Dopamine turn-over rates were unaltered. Plasma catecholamine and corticosterone levels were unaltered. Intraperitoneal injections of 10 mg/kg of the KCa3.1/KCa2-activator SKA-31 reduced rearing and turning behavior in KCa3.1(+/+) but not in KCa3.1(-/-) mice, while 30 mg/kg SKA-31 caused strong sedation in 50% of the animals of either genotypes. KCa3.1(-/-) mice were hyperactive (≈+60%) in their home cage and SKA-31-administration reduced nocturnal physical activity in KCa3.1(+/+) but not in KCa3.1(-/-) mice.Conclusions/significanceKCa3.1-deficiency causes locomotor hyperactivity and altered monoamine levels in selected brain regions, suggesting a so far unknown functional link of KCa3.1 channels to behavior and monoaminergic neurotransmission in mice. The tranquilizing effects of low-dose SKA-31 raise the possibility to use KCa3.1/KCa2 channels as novel pharmacological targets for the treatment of neuropsychiatric hyperactivity disorders.
Databáze: OpenAIRE
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